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.     

Do nanoparticles present ecotoxicological risks for the health of the aquatic environment?

Nanotechnology is a major innovative scientific and economic growth area, which may present a variety of hazards for environmental and human health. The surface properties and very small size of nanoparticles and nanotubes provide surfaces that may bind and transport toxic chemical pollutants, as well as possibly being toxic in their own right by generating reactive radicals. There is a wealth of evidence for the harmful effects of nanoscale combustion-derived particulates (ultrafines), which when inhaled can cause a number of pulmonary pathologies in mammals and humans. However, release of manufactured nanoparticles into the aquatic environment is largely an unknown. This review addresses the possible hazards associated with nanomaterials and harmful effects that may result from exposure of aquatic animals to nanoparticles. Possible nanoparticle association with naturally occurring colloids and particles is considered together with how this could affect their bioavailability and uptake into cells and organisms. Uptake by endocytotic routes are identified as probable major mechanisms of entry into cells; potentially leading to various types of toxic cell injury. The higher level consequences for damage to animal health, ecological risk and possible food chain risks for humans are also considered based on known behaviours and toxicities for inhaled and ingested nanoparticles in the terrestrial environment. It is concluded that a precautionary approach is required with individual evaluation of new nanomaterials for risk to the health of the environment. Although current toxicity testing protocols should be generally applicable to identify harmful effects associated with nanoparticles, research into new methods is required to address the special properties of nanomaterials.     

Frameworks and tools for risk assessment of manufactured nanomaterials

Commercialization of nanotechnologies entails a regulatory requirement for understanding their environmental, health and safety (EHS) risks. Today we face challenges to assess these risks, which emerge from uncertainties around the interactions of manufactured nanomaterials (MNs) with humans and the environment. In order to reduce these uncertainties, it is necessary to generate sound scientific data on hazard and exposure by means of relevant frameworks and tools. The development of such approaches to facilitate the risk assessment (RA) of MNs has become a dynamic area of research. The aim of this paper was to review and critically analyse these approaches against a set of relevant criteria. The analysis concluded that none of the reviewed frameworks were able to fulfill all evaluation criteria. Many of the existing modelling tools are designed to provide screening-level assessments rather than to support regulatory RA and risk management. Nevertheless, there is a tendency towards developing more quantitative, higher-tier models, capable of incorporating uncertainty into their analyses. There is also a trend towards developing validated experimental protocols for material identification and hazard testing, reproducible across laboratories. These tools could enable a shift from a costly case-by-case RA of MNs towards a targeted, flexible and efficient process, based on grouping and read-across strategies and compliant with the 3R (Replacement, Reduction, Refinement) principles. In order to facilitate this process, it is important to transform the current efforts on developing databases and computational models into creating an integrated data and tools infrastructure to support the risk assessment and management of MNs.     

GRADE: Assessing the quality of evidence in environmental and occupational health

There is high demand in environmental health for adoption of a structured process that evaluates and integrates evidence while making decisions and recommendations transparent. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework holds promise to address this demand. For over a decade, GRADE has been applied successfully to areas of clinical medicine, public health, and health policy, but experience with GRADE in environmental and occupational health is just beginning. Environmental and occupational health questions focus on understanding whether an exposure is a potential health hazard or risk, assessing the exposure to understand the extent and magnitude of risk, and exploring interventions to mitigate exposure or risk. Although GRADE offers many advantages, including its flexibility and methodological rigor, there are features of the different sources of evidence used in environmental and occupational health that will require further consideration to assess the need for method refinement. An issue that requires particular attention is the evaluation and integration of evidence from human, animal, in vitro, and in silico (computer modeling) studies when determining whether an environmental factor represents a potential health hazard or risk. Assessment of the hazard of exposures can produce analyses for use in the GRADE evidence-to-decision (EtD) framework to inform risk-management decisions about removing harmful exposures or mitigating risks. The EtD framework allows for grading the strength of the recommendations based on judgments of the certainty in the evidence (also known as quality of the evidence), as well as other factors that inform recommendations such as social values and preferences, resource implications, and benefits. GRADE represents an untapped opportunity for environmental and occupational health to make evidence-based recommendations in a systematic and transparent manner. The objectives of this article are to provide an overview of GRADE, discuss GRADE's applicability to environmental health, and identify priority areas for method assessment and development.     

A spatial risk assessment methodology to support the remediation of contaminated land

When soil and groundwater contaminations occur over large areas, remediation measures should be spatially prioritized on the basis of the risk posed to human health and in compliance with technological and budget constraints. Within this scope, the application of human health risk assessment algorithms in a spatially resolved environment raises a number of methodological and technical complexities. In this paper, a methodology is proposed and applied in a case study to support the entire formulation process of remediation plans, encompassing hazard assessment, exposure assessment, risk characterisation, uncertainty assessment and allocation of risk reduction measures. In the hazard assessment, it supports the selection of Contaminants of Concern (CoC) with regard to both their average concentrations and peak concentrations, i.e. hot spots. In the exposure assessment, it provides a zoning of the site based on the geostatistical mapping of contaminant. In the risk characterisation, it generates vector maps of Risk Factors on the basis of the risk posed by multiple substances and allows the interrogation of most relevant CoC and exposure pathways for each zone of the site. It also supports the Monte Carlo based probabilistic estimation of the Risk Factors and generates maps of the associated uncertainty. In the risk reduction phase, it supports the formulation of remediation plans based on the stepwise spatial allocation of remediation interventions and the on-time simulation of risk reduction performances. The application of this methodology is fully supported by an easy-to-use and customized Geographical Information System and does not require high expertise for interpretation. The proposed methodology is the core module of a Decision Support System (DSS) that was implemented in the DESYRE software aimed at supporting the risk-based remediation of megasites.     

Integration of environmental and human health risk assessment for industries using hazardous materials: a quantitative multi criteria approach for environmental decision makers

Environmental management, for which environmental and human health risk assessment is the first stage, is a requirement for industries both before construction and during operation in order to sustain improved quality of life in the ecosystem. Therefore, the aim of this study is to propose an approach that integrates environmental and human health risk assessment for industries using hazardous materials in order to support environmental decision makers with quantitative and directive results. Analytic hierarchy process and fuzzy logic are used as tools to handle problems caused by complexity of environment and uncertain data. When the proposed approach is implemented to a scenario, it was concluded that it is possible to define risk sources with their risk classes and related membership degrees in that classes which enable the decision maker to decide which risk source has priority. In addition, they can easily point out and rank the factors contributing those risk sources owing to priority weights of them. As a result, environmental decision makers can use this approach while they are developing management alternatives for unfounded and on-going industrial plants using hazardous materials.     

PestScreen: a screening approach for scoring and ranking pesticides by their environmental and toxicological concern

A chemical ranking and scoring method entitled PestScreen has been developed as a screening tool to provide a relative assessment of pesticide hazards to human health and the environment. The method was developed to serve as an analytical tool in screening and identification of pesticides of environmental concern used in agriculture. PestScreen incorporates both the toxic effects of pesticides and their fate and exposure characteristics in different compartments of the environment. This is done by combining measures of chemical toxicity pertaining to both human health and the environment with chemical release amounts and information on overall environmental persistence, long-range transport potential and human population intake fractions. Each hazard measure is scored and weighted and finally combined with the pesticide application dose to provide a single final indicator of relative concern (PestScore). Results for 217 pesticides are presented and the practical implementation is illustrated on behalf of three practical case studies.     

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.     

Application of cattle manure as fertilizer in pastureland: estimating the incremental risk due to metal accumulation employing a multicompartment model

Specific-site data of metal concentration in cattle manure from NW Spain and a multicompartment fate and exposure model were used to evaluate metal fate and the main routes of exposure after a 100 year period of application of cattle manure as fertiliser in pastureland. Risk assessment was performed as a probabilistic analysis, and using a conservative worst-case exposure scenario. An accumulation model was used to predict the metal concentration in each environmental medium of concern. The incremental risk was estimated for the population inhabiting the surroundings of the area by a general multiexposure model. Monte Carlo simulations were performed to analyse uncertainty of the results. Furthermore, a sensitivity analysis was carried out to identify the contribution to variance by the different metals and exposure routes. Among the five pathways evaluated, the ingestion of meat and milk from cattle grazing in the area represents the main contribution to total exposure. The results indicate that the incremental risk to human health for people living in the surroundings of pasturelands due to continuous application of cattle manure after a 100 year period are not negligible for the metals considered (Cd, Cu, Ni, Pb and Zn), posing a total Reasonable Maximum Exposure (RME) of 0.75, being the ingestion of meat the main exposure pathway.     

Cumulative health risk assessment of 17 perfluoroalkylated and polyfluoroalkylated substances (PFASs) in the Swedish population

Humans are simultaneously exposed to a multitude of chemicals. Human health risk assessment of chemicals is, however, normally performed on single substances, which may underestimate the total risk, thus bringing a need for reliable methods to assess the risk of combined exposure to multiple chemicals. Per- and polyfluoroalkylated substances (PFASs) is a large group of chemicals that has emerged as global environmental contaminants. In the Swedish population, 17 PFASs have been measured, of which the vast majority lacks human health risk assessment information. The objective of this study was to for the first time perform a cumulative health risk assessment of the 17 PFASs measured in the Swedish population, individually and in combination, using the Hazard Index (HI) approach. Swedish biomonitoring data (blood/serum concentrations of PFASs) were used and two study populations identified: 1) the general population exposed indirectly via the environment and 2) occupationally exposed professional ski waxers. Hazard data used were publicly available toxicity data for hepatotoxicity and reproductive toxicity as well as other more sensitive toxic effects. The results showed that PFASs concentrations were in the low ng/ml serum range in the general population, reaching high ng/ml and low μg/ml serum concentrations in the occupationally exposed. For those congeners lacking toxicity data with regard to hepatotoxicity and reproductive toxicity read-across extrapolations was performed. Other effects at lower dose levels were observed for some well-studied congeners. The risk characterization showed no concern for hepatotoxicity or reproductive toxicity in the general population except in a subpopulation eating PFOS-contaminated fish, illustrating that high local exposure may be of concern. For the occupationally exposed there was concern for hepatotoxicity by PFOA and all congeners in combination as well as for reproductive toxicity by all congeners in combination, thus a need for reduced exposure was identified. Concern for immunotoxicity by PFOS and for disrupted mammary gland development by PFOA was identified in both study populations as well as a need of additional toxicological data for many PFAS congeners with respect to all assessed endpoints.     

Health and environmental costs of pesticide use in vegetable farming in Nepal

There is a growing concern of pesticide risks to human health, natural environment and ecosystems. Many previous economic valuations have accounted health aspects or environmental components, but rarely combined; thus, overall risk assessment is partially distorted. The study, conducted close to the capital of Nepal, addressed the health effects of pesticides on small-scale farmers and evaluated the monetary risks of pesticide use on human health and environmental resources. We also aim to establish the relationships among valuation methods. The paper adopts cost of illness, defensive expenditure and contingent valuation willingness to pay approach. The study concluded that the methods used for valuing pesticide risks to human and environmental health are theoretically consistent. The exposed individuals are likely to bear significant economic costs of exposures depending on geographical location, pesticide use magnitudes and frequency. Individuals are willing to pay between 53 and 79% more than the existing pesticide price to protect their health and environment. The integrated pest management training is less likely to reduce health costs of pesticide exposure, although it leads to higher investment in safety measures.     

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.     

How to assess exposure of aquatic organisms to manufactured nanoparticles?

Ecological risk of chemicals is measured by the quotient of predicted no-effect concentrations and predicted exposure concentrations, which are hard to assess for manufactured nanomaterials (NMs). This paper proposes modifications to currently used models, in order to make them suitable for estimating exposure concentrations of NMs in the aquatic environment. We have evaluated the adequacy of the current guidance documents for use with NMs and conclude that nano-specific fate processes, such as sedimentation and dissolution need to be incorporated. We have reviewed the literature on sedimentation and dissolution of NMs in environmentally relevant systems. We deduce that the overall kinetics of water-sediment transport of NMs should be close to first order. The lack of data on dissolution of NMs under environmentally realistic conditions calls for a pragmatic decision on which rates to be used in modeling. We find that first order removal kinetics for dissolution seems adequate. Based on limited data from literature, probable removal rates range from 0 to 10(-4)s(-1) for sedimentation, and from 0 to 10(-5)s(-1) for dissolution. Further experimental data at environmentally relevant conditions for sedimentation and dissolution of NMs is needed.     

Public health benefits of compliance with current E.U. emissions standards for municipal waste incinerators: a health risk assessment with the CalTox multimedia exposure model

The Angers municipal solid waste incineration plant, in operation since 1974, was upgraded in 2000 to comply with new European standards. This article discusses the risks associated with past and present emissions from the incinerator and its nearby furnace. Emissions of SO(2), HCl, particulate matter, lead, mercury, cadmium and dioxins were studied. We characterised the risks associated with exposure via inhalation and ingestion of locally grown products, before and after the upgrade. Emissions were estimated from regulatory measurements, and ambient air concentrations estimated with a Gaussian dispersion model. The CalTox multimedia model was used to calculate concentrations in the food chain. Food intake rates came from a nationwide survey. Inhalation exposure to respiratory irritants produced a hazard ratio less than 1 in all scenarios, except for SO(2) in the immediate neighbourhood of the incinerator, before the change in furnace fuel and in case of high-pressure weather conditions. The individual excess risk of cancer was less than 10(-6) and the hazard ratios for metals were less than 1. Before compliance, the average dioxin exposure attributable to the incinerator accounted for roughly one quarter of the average total exposure from traffic and other combustion activities. Although the corresponding hazard ratio was less than 1, the individual lifetime excess risk, assuming no change in emissions, was 2 x 10(-4). After compliance, all hazard ratios and future individual lifetime excess risks appear minimal. These results are consistent with environmental data and other studies, but many uncertainties remain, such as intermedia transfer coefficients for dioxins. Nevertheless compliance has vastly reduced the probability of health effects.     

Radon releases from Australian uranium mining and milling projects: assessing the UNSCEAR approach

The release of radon gas and progeny from the mining and milling of uranium-bearing ores has long been recognised as a potential radiological health hazard. The standards for exposure to radon and progeny have decreased over time as the understanding of their health risk has improved. In recent years there has been debate on the long-term releases (10,000 years) of radon from uranium mining and milling sites, focusing on abandoned, operational and rehabilitated sites. The primary purpose has been estimates of the radiation exposure of both local and global populations. Although there has been an increasing number of radon release studies over recent years in the USA, Australia, Canada and elsewhere, a systematic evaluation of this work has yet to be published in the international literature. This paper presents a detailed compilation and analysis of Australian studies. In order to quantify radon sources, a review of data on uranium mining and milling wastes in Australia, as they influence radon releases, is presented. An extensive compilation of the available radon release data is then assembled for the various projects, including a comparison to predictions of radon behaviour where available. An analysis of cumulative radon releases is then developed and compared to the UNSCEAR approach. The implications for the various assessments of long-term releases of radon are discussed, including aspects such as the need for ongoing monitoring of rehabilitation at uranium mining and milling sites and life-cycle accounting.     

Radioactive particles in dose assessments

Radioactive particles present a novel exposure pathway for members of the public. For typical assessments of potential doses received by members of the public, habit surveys and environmental monitoring combine to allow the assessment to occur. In these circumstances it is believed that the probability of encounter/consumption is certain. The potential detriment is assessed through sampling the use of environmental monitoring data and dose coefficients such as that in ICRP 60 [ICRP, 1990. 1990 Recommendations of the international commission on radiological protection. Publication 60. Annals of the ICRP 21 (1-3)]. However, radioactive particles often represent a hazard that is difficult to quantify and where the probability of encounter is less than certain as are the potential effects on health. Normal assessment methodologies through sampling and analysis are not appropriate for assessing the impact of radioactive particles either prospectively or retrospectively. This paper details many of the issues that should be considered when undertaking an assessment of the risk to health posed by radioactive particles.     

Cumulative risk assessment of chemical exposures in urban environments

We performed a cumulative risk assessment for people living in a hypothetical urban environment, called Urbania. The main aims of the study were to demonstrate how a cumulative risk assessment for a middle-sized European city can be performed and to identify the bottlenecks in terms of data availability and knowledge gaps. The assessment focused on five air pollutants (i.e., PM??, benzene, toluene, nonane and naphthalene) and six food pesticides (i.e., acetamiprid, carbendazim, chlorpyrifos, diazinon, imidacloprid and permethrin). Exposure predictions showed that PM??, benzene and naphthalene exposure frequently exceeded the standards, and that the indoor environment contributed more than the outdoor environment. Effect predictions showed that mixture and interaction effects were generally limited. However, model calculations indicated potential synergistic effects between naphthalene and benzene and between chlorpyrifos, diazinon and toluene. PM?? dominated the health impact expressed in Disability Adjusted Life Years (DALYs). We conclude that measures to reduce the health impact of environmental pollution should focus on the improvement of indoor air quality and the reduction of PM?? emissions. Cumulative risk assessment can be improved by (1) the development of person-oriented exposure models that can simulate the cumulative exposure history of individuals, (2) a better mechanistic understanding of the effects of cumulative stressors, and (3) the development of instruments to prioritize stressors for inclusion in cumulative risk assessments.     

城市土壤重金属含量及其对儿童健康风险的初步评价——以四川省宜宾市为例

通过对宜宾市主要街道47个土壤样中Pb、As、Zn和Cu含量的调查研究，并利用健康风险评价模型，初步评价了城市土壤中重金属对儿童(6~12岁)的健康风险。Pb、Zn和Cu采用火焰 原子吸收光谱仪测定，As采用氢化物发生 原子荧光光谱测定。结果表明，宜宾市城市土壤中Pb、Zn和Cu含量显著高于四川省土壤背景值，表现出明显的累积效应(〖WTBX〗p〖WTBZ〗=0000)，As含量显著低于四川省土壤背景值(〖WTBX〗p〖WTBZ〗=002)；与四川省土壤基线值相比，土壤中Pb、Zn和Cu含量的超标率分别为362%、297%和511%，As含量尚未超标。城市土壤中Pb、As、Zn和Cu的单危害指数大小(〖WTBX〗HI)依次为HIAs>HIPb>HICu>HIZn，总危害指数THI〖WTBZ〗为346×10-1。单危害指数和总危害指数均低于可接受水平1，未对儿童表现出非致癌危害。土壤中As的总致癌风险〖WTBX〗TCR〖WTBZ〗为872×10-6，在可接受水平内(1×10-6~1×10-4)，未对儿童表现出致癌风险。