A critical review of frameworks used for evaluating reliability and relevance of (eco)toxicity data: Perspectives for an integrated eco-human decision-making framework

Considerable efforts have been invested so far to evaluate and rank the quality and relevance of (eco)toxicity data for their use in regulatory risk assessment to assess chemical hazards. Many frameworks have been developed to improve robustness and transparency in the evaluation of reliability and relevance of individual tests, but these frameworks typically focus on either environmental risk assessment (ERA) or human health risk assessment (HHRA), and there is little cross talk between them. There is a need to develop a common approach that would support a more consistent, transparent and robust evaluation and weighting of the evidence across ERA and HHRA. This paper explores the applicability of existing Data Quality Assessment (DQA) frameworks for integrating environmental toxicity hazard data into human health assessments and vice versa. We performed a comparative analysis of the strengths and weaknesses of eleven frameworks for evaluating reliability and/or relevance of toxicity and ecotoxicity hazard data. We found that a frequent shortcoming is the lack of a clear separation between reliability and relevance criteria. A further gaps and needs analysis revealed that none of the reviewed frameworks satisfy the needs of a common eco-human DQA system. Based on our analysis, some key characteristics, perspectives and recommendations are identified and discussed for building a common DQA system as part of a future integrated eco-human decision-making framework. This work lays the basis for developing a common DQA system to support the further development and promotion of Integrated Risk Assessment.     

Traffic-related fine and ultrafine particle exposures of professional drivers and illness: An opportunity to better link exposure science and epidemiology to address an occupational hazard?

Exposures to traffic-related air pollution (TRAP) can be particularly high in transport microenvironments (i.e. in and around vehicles) despite the short durations typically spent there. There is a mounting body of evidence that suggests that this is especially true for fine (< 2.5 µm) and ultrafine (< 100 nm, UF) particles. Professional drivers, who spend extended periods of time in transport microenvironments due to their job, may incur exposures markedly higher than already elevated non-occupational exposures. Numerous epidemiological studies have shown a raised incidence of adverse health outcomes among professional drivers, and exposure to TRAP has been suggested as one of the possible causal factors. Despite this, data describing the range and determinants of occupational exposures to fine and UF particles are largely conspicuous in their absence. Such information could strengthen attempts to define the aetiology of professional drivers' illnesses as it relates to traffic combustion-derived particles.In this article, we suggest that the drivers' occupational fine and UF particle exposures are an exemplar case where opportunities exist to better link exposure science and epidemiology in addressing questions of causality. The nature of the hazard is first introduced, followed by an overview of the health effects attributable to exposures typical of transport microenvironments. Basic determinants of exposure and reduction strategies are also described, and finally the state of knowledge is briefly summarised along with an outline of the main unanswered questions in the topic area.     

Analysis of currently available data for characterising the risk of engineered nanomaterials to the environment and human health--lessons learned from four case studies

Production volumes and the use of engineered nanomaterials in many innovative products are continuously increasing, however little is known about their potential risk for the environment and human health. We have reviewed publicly available hazard and exposure data for both, the environment and human health and attempted to carry out a basic risk assessment appraisal for four types of nanomaterials: fullerenes, carbon nanotubes, metals, and metal oxides (ENRHES project 2009(1)). This paper presents a summary of the results of the basic environmental and human health risk assessments of these case studies, highlighting the cross cutting issues and conclusions about fate and behaviour, exposure, hazard and methodological considerations. The risk assessment methodology being the basis for our case studies was that of a regulatory risk assessment under REACH (ECHA, 2008(2)), with modifications to adapt to the limited available data. If possible, environmental no-effect concentrations and human no-effect levels were established from relevant studies by applying assessment factors in line with the REACH guidance and compared to available exposure data to discuss possible risks. When the data did not allow a quantitative assessment, the risk was assessed qualitatively, e.g. for the environment by evaluating the information in the literature to describe the potential to enter the environment and to reach the potential ecological targets. Results indicate that the main risk for the environment is expected from metals and metal oxides, especially for algae and Daphnia, due to exposure to both, particles and ions. The main risks for human health may arise from chronic occupational inhalation exposure, especially during the activities of high particle release and uncontrolled exposure. The information on consumer and environmental exposure of humans is too scarce to attempt a quantitative risk characterisation. It is recognised that the currently available database for both, hazard and exposure is limited and there are high uncertainties in any conclusion on a possible risk. The results should therefore not be used for any regulatory decision making. Likewise, it is recognised that the REACH guidance was developed without considering the specific behaviour and the mode of action of nanomaterials and further work in the generation of data but also in the development of methodologies is required.     

Approaches for describing and communicating overall uncertainty in toxicity characterizations: U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) as a case study

Single point estimates of human health hazard/toxicity values such as a reference dose (RfD) are generally used in chemical hazard and risk assessment programs for assessing potential risks associated with site- or use-specific exposures. The resulting point estimates are often used by risk managers for regulatory decision-making, including standard setting, determination of emission controls, and mitigation of exposures to chemical substances. Risk managers, as well as stakeholders (interested and affected parties), often have limited information regarding assumptions and uncertainty factors in numerical estimates of both hazards and risks. Further, the use of different approaches for addressing uncertainty, which vary in transparency, can lead to a lack of confidence in the scientific underpinning of regulatory decision-making. The overarching goal of this paper, which was developed from an invited participant workshop, is to offer five approaches for presenting toxicity values in a transparent manner in order to improve the understanding, consideration, and informed use of uncertainty by risk assessors, risk managers, and stakeholders. The five approaches for improving the presentation and communication of uncertainty are described using U.S. Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) as a case study. These approaches will ensure transparency in the documentation, development, and use of toxicity values at EPA, the Agency for Toxic Substances and Disease Registry (ATSDR), and other similar assessment programs in the public and private sector. Further empirical testing will help to inform the approaches that will work best for specific audiences and situations.     

Using GRADE to respond to health questions with different levels of urgency

Increasing interest exists in applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to environmental health evidence. While ideally applied to evidence synthesized in systematic reviews and corresponding summary tables, such as evidence profiles, GRADE's correct application requires that “the evidence that was assessed and the methods that were used to identify and appraise that evidence should be clearly described.” In this article, we suggest that GRADE could be applied to evidence assembled from narrative reviews, modelled (indirect) evidence, or evidence assembled as part of a rapid response, if the underlying judgments about the certainty in this evidence are based on the relevant GRADE domains and provided transparently. Health questions that require assessing the certainty in a body of evidence to provide trustworthy answers may range from hours, to days or weeks, to a few months to scenarios that allow assessing evidence without short-term time pressures. Time frames of emergent, urgent or rapid evidence assessments will often require relying on existing summaries or rapidly compiling the available evidence and making assessments. Even without available full systematic reviews, expressing the certainty in the evidence can provide useful guidance for users of the evidence and those who evaluate certainty in effects. The ratings also help clarifying disagreement between organizations tackling similar questions about the evidence. Using the structured GRADE domains, narrative or other summaries of the evidence can be presented transparently.     

Pollutant exposures and health symptoms in aircrew and office workers: Is there a link?

Sensory effects in eyes and airways are common symptoms reported by aircraft crew and office workers. Neurological symptoms, such as headache, have also been reported. To assess the commonality and differences in exposures and health symptoms, a literature search of aircraft cabin and office air concentrations of non-reactive volatile organic compounds (VOCs) and ozone-initiated terpene reaction products were compiled and assessed. Data for tricresyl phosphates, in particular tri-ortho-cresyl phosphate (ToCP), were also compiled, as well as information on other risk factors such as low relative humidity.A conservative health risk assessment for eye, airway and neurological effects was undertaken based on a “worst-case scenario” which assumed a simultaneous constant exposure for 8 h to identified maximum concentrations in aircraft and offices. This used guidelines and reference values for sensory irritation for eyes and upper airways and airflow limitation; a tolerable daily intake value was used for ToCP. The assessment involved the use of hazard quotients or indexes, defined as the summed ratio(s) (%) of compound concentration(s) divided by their guideline value(s).The concentration data suggest that, under the assumption of a conservative “worst-case scenario”, aircraft air and office concentrations of the compounds in question are not likely to be associated with sensory symptoms in eyes and airways. This is supported by the fact that maximum concentrations are, in general, associated with infrequent incidents and brief exposures. Sensory symptoms, in particular in eyes, appear to be exacerbated by environmental and occupational conditions that differ in aircraft and offices, e.g., ozone incidents, low relative humidity, low cabin pressure, and visual display unit work. The data do not support airflow limitation effects. For ToCP, in view of the conservative approach adopted here and the rareness of reported incidents, the health risk of exposure to this compound in aircraft is considered negligible.     

Modelling microbial health risk of wastewater reuse: A systems perspective

There is a widespread need for the use of quantitative microbial risk assessment (QMRA) to determine reclaimed water quality for specific uses, however neither faecal indicator levels nor pathogen concentrations alone are adequate for assessing exposure health risk. The aim of this study was to build a conceptual model representing factors contributing to the microbiological health risks of reusing water treated in maturation ponds. This paper describes the development of an unparameterised model that provides a visual representation of theoretical constructs and variables of interest. Information was collected from the peer-reviewed literature and through consultation with experts from regulatory authorities and academic disciplines. In this paper we explore how, considering microbial risk as a modular system, following the QMRA framework enables incorporation of the many factors influencing human exposure and dose response, to better characterise likely human health impacts. By using and expanding upon the QMRA framework we deliver new insights into this important field of environmental exposures. We present a conceptual model of health risk of microbial exposure which can be used for maturation ponds and, more importantly, as a generic tool to assess health risk in diverse wastewater reuse scenarios.     

Exposure to bushfire smoke during prescribed burns and wildfires: firefighters' exposure risks and options

Firefighters are exposed to known health-damaging air pollutants present in bushfire smoke and poorly managed exposure can result in serious health issues. A better understanding of exposure levels and the major factors influencing exposures is crucial for the development of mitigation strategies to minimise exposure risks and adverse health impacts. This study monitored air toxics within the breathing zone of firefighters at prescribed burns and at wildfires in Australia. The results showed that exposure levels were highly variable, with higher exposures (sometimes exceeding occupational exposure standards) associated with particular work tasks (such as patrol and suppression) and with certain burn conditions. The majority of firefighter's exposures were at low and moderate levels (~60%), however considerable attention should be given to the high (~30%) and very high (6%) exposure risk situations for which acute and chronic health risks are very likely and for which control strategies should be developed and implemented to minimise health risks.     

城市土地置换过程中土壤多环芳烃污染的健康风险评价

利用健康风险评价方法判定污染土壤是否需要修复或再次开发已成为一个新的研究领域。以某区域土地置换开发为案例，结合区域未来土地利用类型，采用健康风险评价模型对土壤多环芳烃（PAHs）污染可能给未来入住人群带来的健康风险进行初步评价。结果显示，在正常情况与极端情况两种暴露场合下，考虑直接接触不慎摄入、呼吸土壤尘和皮肤直接接触土壤3种途径，计算出的土壤PAHs污染的致癌风险相对较高，部分点位已经超过了人体健康可接受的致癌风险程度。且以敏感人群儿童为例，利用摄入量和风险评价反推得出，当土壤中PAHs含量低于634 μg/kg时，在极端情况下，儿童致癌风险可降低到可接受的致癌风险水平。随着环境管理工作的深入发展，在城市土地置换过程中应逐步加强环境健康风险评价方面的研究。     

Uncertainties in human health risk assessment of environmental contaminants: A review and perspective

Addressing uncertainties in human health risk assessment is a critical issue when evaluating the effects of contaminants on public health. A range of uncertainties exist through the source-to-outcome continuum, including exposure assessment, hazard and risk characterisation. While various strategies have been applied to characterising uncertainty, classical approaches largely rely on how to maximise the available resources. Expert judgement, defaults and tools for characterising quantitative uncertainty attempt to fill the gap between data and regulation requirements. The experiences of researching 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) illustrated uncertainty sources and how to maximise available information to determine uncertainties, and thereby provide an ‘adequate’ protection to contaminant exposure. As regulatory requirements and recurring issues increase, the assessment of complex scenarios involving a large number of chemicals requires more sophisticated tools. Recent advances in exposure and toxicology science provide a large data set for environmental contaminants and public health. In particular, biomonitoring information, in vitro data streams and computational toxicology are the crucial factors in the NexGen risk assessment, as well as uncertainties minimisation. Although in this review we cannot yet predict how the exposure science and modern toxicology will develop in the long-term, current techniques from emerging science can be integrated to improve decision-making.     

Community mercury levels in the vicinity of peri-urban waste disposal sites and fossil fuel burning operations

INTRODUCTION: A study was conducted as a result of concern about mercury absorption amongst residents of a peri-urban area in Cape Town, South Africa, in close proximity to waste disposal sites and an industrial area. STUDY METHODS: The study compared urine mercury concentrations in a random sample of adult residents and children in both the formal and informal housing settlements of the "exposure" area (n = 90) and a control area (n = 90). A short questionnaire elicited demographic, lifestyle and medical details and possible occupational, household and environmental mercury exposures. RESULTS: The two samples were comparable with respect to background and potential confounding variables. The prevalence of urinary mercury levels>or=the WHO reference range in the exposure area was also higher than that in the control area (13% vs. 0%). The median urinary mercury concentrations in both study areas were below the World Health Organisation (WHO) reference level of 5.0 microg/g creatinine. The median level in the exposure area was slightly, but statistically significantly, higher than in the control area (1.1 vs. 0.25 microg/g creatinine), and the excess persisted after controlling for known possible mercury exposures. CONCLUSIONS: This is to our knowledge the first study of community inorganic mercury absorption in a developing country setting, and where airborne mercury was the exposure of concern. It was concluded that the health risk associated with the urinary mercury levels of residents in the exposure area was very low. However, low level environmental exposure in the area of concern could not be excluded.     

Occupational exposure of phosphate mine workers: airborne radioactivity measurements and dose assessment

Under the Egyptian program for radiation safety and control, airborne radioactivity measurements and radiological dose assessment were conducted in some phosphate and uranium mines. Abu-Tartor mine is one of the biggest underground phosphate mines in Egypt. Airborne radioactivity, radon ((222)Rn) and its short-lived decay products (progenies) and thoron ((220)Rn), were measured in selected locations along the mine. The environmental gamma and workers dose equivalent rate (mSv/y) were measured inside and outside the mine using thermo-luminescence dosimeters (TLD). The results were presented and discussed. The calculated annual effective dose due to airborne radioactivity is the main source of occupational exposure and exceeding the maximum recommended level by ICRP-60 inside the mine tunnels. A number of recommendations are suggested to control the occupational exposures.     

The formal electronic recycling industry: Challenges and opportunities in occupational and environmental health research

BackgroundE-waste includes electrical and electronic equipment discarded as waste without intent of reuse. Informal e-waste recycling, typically done in smaller, unorganized businesses, can expose workers and communities to serious chemical health hazards. It is unclear if formalization into larger, better-controlled electronics recycling (e-recycling) facilities solves environmental and occupational health problems.ObjectivesTo systematically review the literature on occupational and environmental health hazards of formal e-recycling facilities and discuss challenges and opportunities to strengthen research in this area.MethodsWe identified 37 publications from 4 electronic databases (PubMed, Web of Science, Environmental Index, NIOSHTIC-2) specific to chemical exposures in formal e-recycling facilities.DiscussionEnvironmental and occupational exposures depend on the degree of formalization of the facilities but further reduction is needed. Reported worker exposures to metals were often higher than recommended occupational guidelines. Levels of brominated flame-retardants in worker's inhaled air and biological samples were higher than those from reference groups. Air, dust, and soil concentrations of metals, brominated flame-retardants, dioxins, furans, polycyclic-aromatic hydrocarbons, or polychlorinated biphenyls found inside or near the facilities were generally higher than reference locations, suggesting transport into the environment. Children of a recycler had blood lead levels higher than public health recommended guidelines.ConclusionsWith mounting e-waste, more workers, their family members, and communities could experience unhealthful exposures to metals and other chemicals. We identified research needs to further assess exposures, health, and improve controls. The long-term solution is manufacturing of electronics without harmful substances and easy-to-disassemble components.     

An approach to comparative assessments of potential health risks from exposure to radionuclides and hazardous chemicals

The need to compare potential health risks to the public associated with different activities that can result in releases of hazardous substances to the environment is becoming increasingly important in decision-making. In making such comparisons, it is desirable to use equivalent indicators of potential health risks for radionuclides, chemical carcinogens, and noncarcinogenic hazardous chemicals. Current approaches to risk assessment that were developed for purposes of protecting human health do not provide equivalent indicators of potential risks from exposure to radionuclides and hazardous chemicals. Comparisons of environmental concentrations or calculated exposures or risks with standards for protection of public health also do not provide equivalent indicators of potential risks. We propose a simple approach to comparative risk assessments in which calculated exposures to any hazardous substances are expressed relative to no-observed-effect levels (NOELs) or, preferably, lower confidence limits of benchmark doses (BMDLs) in humans. This approach provides an equivalent, science-based indicator of the relative risks posed by different exposures to any hazardous substances.     

Using the Framework for Integrated Sustainability Assessment (FISA) to expand the Multiregional Input–Output analysis to account for the three pillars of sustainability

Decision makers interested in promoting sustainable development must simultaneously consider the environmental, economic and social implications of any action. This article proposes the Framework for Integrated Sustainability Assessment (FISA), a methodological framework for conducting a sustainability impact assessment of any investment project. Based on a Multiregional Input–Output (MRIO) framework, FISA links the extended MRIO results with social risk data from the Social Hotspots Database (SHDB) in order to integrate the social with the environmental and economic pillars. Resulting impacts are simultaneously considered and reported by means of FISA charts, making it possible to assess the different impacts within the three sustainability pillars across countries involved in the whole supply chain of investment projects. This methodological framework can be applied not only to compare the sustainability impacts of two alternative projects, but also to derive specific recommendations aimed at minimizing the harmful social, environmental and economic effects along the whole project supply chain.     

Concepts of human exposure to air pollution

In recent years, considerable attention has focused on the concept of “human exposure” to environmental pollutants, but different investigators seem to have developed different definitions of this concept and used different approaches for estimating it. This paper reviews a number of “exposure” studies in a single environmental medium—air pollution—to see how others have defined this concept in the literature. Many previous investigators unfortunately calculate “exposures” by relying on data from fixed air monitoring stations, and they assume that people are located in the same place, usually their residential address, throughout a 24-h period. However, a second body of literature shows that fixed air monitoring stations do not necessarily reflect human exposures, because concentrations observed indoors—in homes, offices, factories, and motor vehicles—differ from those observed at fixed stations, and people usually spend considerable time in these locations. In an effort to standardize the nomenclature dealing with exposures, a definition is proposed in which the pollutant must come into contact with the physical boundary of the person. Then, exposure of person i to pollutant concentration c is viewed as two events occurring jointly: person i is present at a particular location, and concentration c is present at the same location. Mathematical definitions for “integrated exposure,” “average exposure,” and “standardized exposure” with various averaging periods also are introduced. Finally, two different yet compatible research approaches are suggested for determining human exposures to air pollution.     

Pharmaceutical management through environmental product labeling in Sweden

There is an increased awareness that medicinal products for human use may cause negative effects in the environment. In Sweden a voluntary environmental classification system for drugs has been established in collaboration between producers, authorities and the public health care, and used for five years. The idea is to enhance the market demand for medicines with less environmental impact, which in turn will stimulate the producers to design future medicines to be more environmentally friendly. The system is open to the public and based on assessment of the active ingredient in the medicinal product into several classes of risk and hazard, respectively. It is closely related to the EMEA guidelines. Risk is expressed as the ratio between the predicted environmental concentration (PEC) of the active ingredient (AI) and its predicted no effect concentration (PNEC). The hazard is expressed in terms of the AI's persistence, potential to bioaccumulation, and eco-toxicity. Drug data for the classification are delivered by the respective producers.Hitherto more than 300 AI, representing more than 50% of the Swedish volume of drug use, have been classified. Data for risk assessment were missing in 47% of AI. Among drugs with data 7% had a PEC/PNEC ratio > 1, and another 7% had a ratio between 0.1 and 1. The AIs with highest ratio (> 10) were two estrogens. Data for hazard assessment were lacking in 16% of the AI. Among drugs with environmental data 92% were not ready biodegradable, 23% had potential to bioaccumulation, and 61% were toxic to aquatic organisms at a concentration below 1 mg/l. These data are utilized by regional pharmaceutical expert groups when selecting substances to be recommended in public health care in Sweden. They may also be used by prescribing doctors who want to identify the environmentally most favourable substance among several with equivalent medical effect.We conclude that environmental data on human medicinal products are often missing, or reveal unfavourable environmental properties. A proper judgement of the environmental impact of an AI requires a joint evaluation of its risk and hazard. We suggest that the pharmaceutical producers should highlight environmental precaution when designing new AIs, and that the environmental data should be transparent to the general public.     

Association of persistent organic pollutants and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia: A systematic review

BackgroundOver half of the people with diabetes in the world live in Asia. Emerging scientific evidence suggests that diabetes is associated with environmental pollutants, exposures that are also abundant in Asia.ObjectiveTo systematically review the literature concerning the association of persistent organic pollutants (POPs) and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia.MethodsPubMed and Embase were searched to identify studies published up to November 2014. A secondary reference review of all extracted articles and the National Toxicology Program Workshop on the association of POPs with diabetes was also conducted. A total of 19 articles met the inclusion criteria and were evaluated in this review.ResultsTo date, the evidence relating POPs and non-persistent pesticides with diabetes in Asian populations is equivocal. Positive associations were reported between serum concentrations of polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and several organochlorine pesticides (DDT, DDE, oxychlordane, trans-nonachlor, hexachlorobenzene, hexachlorocyclohexane) with diabetes. PCDD/Fs were also associated with blood glucose and insulin resistance, but not beta-cell function. There were substantial limitations of the literature including: most studies were cross-sectional, few studies addressed selection bias and confounding, and most effect estimates had exceptionally wide confidence intervals. Few studies evaluated the effects of organophosphates.ConclusionsWell-conducted research is urgently needed on these pervasive exposures to inform policies to mitigate the diabetes epidemic in Asia.     

Bioavailability links mode of action can improve the long-term field risk assessment for tilapia exposed to arsenic

The objective of this paper was to develop a mechanistic-based framework to explicitly incorporate the factors controlling the bioavailability, toxicodynamics and mode of action to enhance predictive ability of arsenic (As) toxicity to protect the health of farmed tilapia Oreochromis mossambicus. We linked the biotic ligand model and damage assessment model to develop a toxicokinetic model for elucidating the site-specific temporal changes of As bioavailability and to characterize how the fish regulate the metal toxicity. We built a bioavailability-mode of action-based growth toxicity model by linking a bioenergetic growth model and damage assessment model to predict how the As affects on the tilapia growth in the entire life span in site-specific field ecosystems. Here we show that the proposed model well describes the water-chemistry-dependent toxicokinetics and toxicodynamics variations of As to tilapia. We selected two local tilapia farms with different water chemistries located at southwestern Taiwan coast region to implement the proposed algorithm to predict the risk of As exposure. Results indicate that the growth toxicity of O. mossambicus in Taihsi is more sensitive than that in Peimen. We found that the effect of ion competition on the As bioavailability and their ecotoxicological effects on tilapia are more obvious in Taihsi comparing with that in Peimen. We suggested that the proposed bioavailability- and mode of action-based framework can be used to capture the biological response and regulation of tilapia to As exposures. It is applicable for a site-specific and long-term ecotoxicological risk assessment.