A Preliminary Risk Assessment of Human Exposure to Phycotoxins in Shellfish: A Review

Over the past few decades, phycotoxins, secondary metabolites produced by toxic phytoplankton, have seen an increase in their frequency, concentrations, and geographic distribution. As shellfish accumulate phycotoxins making them unfit for human consumption, they are considered as an important food safety issue. Thus, a consumer exposure assessment on phycotoxins is necessary. Exposure assessment requires two types of information: contamination and consumption data. Shellfish contamination data on major toxins encountered by at-risk populations (Domoic Acid group, Okadaic Acid group, and Saxitoxin group) have been reviewed. Consumption data have been reviewed for both general and potential high-consumer populations. Then, we undertook acute and chronic exposure assessments, combining available French contamination data and our own consumption data. Studies including exposure assessment were then reviewed. Lastly, risk characterization was undertaken. It can be concluded that both acute and chronic exposure to phycotoxins via shellfish consumption is a matter of concern, mainly for high consumers identified in this review (specific populations and shellfish harvesters). However, the results for risk characterization must be improved. There is a need for (i) toxicological data to establish a Tolerable Daily Intake; (ii) an assessment of consumption and contamination data, undertaken at the same time, so as to assess exposure.     

Issues in Exposure and Dose Assessment for Epidemiology and Risk Assessment

Epidemiologic studies have been effective in identifying human environmental and occupational hazards. However, most epidemiologic data has been difficult to use in quantitative risk assessments because of the vague specification of exposure and dose. Toxicologic animal studies have used applied doses (quantities administered, or exposures with fixed duration) and well characterized end points to determine effects. However, direct use of animal data in human risk assessment has been limited by uncertainties in the extrapolation. The applied dose paradigm of toxicology is not suited for cross species extrapolation, nor for use in epidemiology as a dose metric because of the complexity of human exposures. Physiologically based pharmacokinetic (PBPK) modeling can estimate the time course of tissue concentrations in humans, given an exposure-time profile, and it has been used for extrapolating findings from animals to humans. It is proposed that human PBPK modeling can be used in appropriately designed epidemiologic studies to estimate tissue concentrations. Secondly, tissue time courses can be used to form dose metrics based on the type and time course of adverse effects. These dose metrics will strengthen the determination of epidemiologic dose-response relationships by reducing misclassification. Findings from this approach can be readily integrated into quantitative risk assessment.     

Distributions for Key Exposure Factors Controlling the Uptake of Xenobiotic Chemicals by Great Blue Herons (Ardea herodius) through Ingestion of Fish

A variety of exposure factors ultimately control the uptake of xenobiotic chemicals by colonial piscivorous birds, such as herons and egrets. These factors, which include feeding rate for various food sources, feeding territory size, and body weight, are critical to the implementation of models commonly used to predict ecological risks. A critical evaluation of literature on avian behavior, physiology, and ecology was conducted in order to identify those variables that most strongly influence uptake of chemicals by herons and egrets. After developing a database of such exposure factors, we identified each factor's range, central tendency, and distribution. Sufficient information was available to allow the development of statistical distributions for body weight, fraction of diet from fish, prey length, distance to foraging site, and feeding territory size for great blue herons. The five distributions presented in this paper are intended to support probabilistic assessments of potential risks to great blue herons. Distributions of exposure factors for great blue herons have not been previously published. Without such data, application of all but the most simple mechanistic models will require point estimates, most of which will be overly conservative and will not support accurate characterization of actual exposures of herons at hazardous waste sites.     

Human Exposure to Malathion during a Possible Vector-Control Intervention against West Nile Virus. I: Methodological Framework for Exposure Assessment

The arrival of West Nile Virus in North America prompted public health authorities to develop intervention plans in order to prevent the propagation of this mosquito-transmitted pathogen. The last-resort measure proposed by the Government of Quebec (Canada) is the large-scale application of insecticides by aerial or ground Ultra Low Volume (ULV) treatment. This article presents an assessment of the exposure to malathion and its metabolite, malaoxon, for a population where an eventual application of malathion would occur. Each exposure pathway is detailed by describing the equation and every conservative assumption. This methodological framework was then used with the aim of assessing the toxicological risk based on a probabilistic approach (see companion article, this issue). In the current study, a daily absorbed dose of the mixture of malathion and malaoxon was estimated in terms of “malathion equivalent dose.” Each exposure pathway following a single event of ground or aerial ULV spraying of malathion was investigated for the population, classified into five age groups. Dermal exposure to dislodgeable residues on turf, foliage, and hard surfaces was estimated to be the most important source of exposure compared to any other pathways; it accounts for 63% to 98% of the estimated cumulative absorbed doses. The hand-to-mouth behavior of toddlers may also contribute considerably to their “malathion-equivalent” exposure (i.e., approximately 15% of the cumulative dose). Otherwise, the current study shows that ground ULV spraying is the type of treatment that may induce lower exposure, because the predicted concentration of malathion on turf and foliar surfaces is less than the one predicted for aerial ULV spraying.     

Ecological Risk Assessment of Radiological Exposure to Depleted Uranium in Soils at a Weapons Testing Facility

The potential for unacceptable risks to biota from radiological exposure to depleted uranium (DU) in soils was evaluated at two sites where DU weapons testing had been conducted in the past. A screening risk assessment was conducted to determine if measured concentrations of DU-associated radionuclides in site soils exceed radionuclide levels considered protective of biota. While concentrations of individual radionuclides did not exceed acceptable levels, total radionuclide concentrations could result in potentially unacceptable doses to exposed biota. Thus, a receptor-specific assessment was conducted to estimate external and internal radiological doses to vegetation and wildlife known or expected to occur at the sites. Wildlife evaluated included herbivores, omnivores, and top-level predators. Internal dose estimates to wildlife considered exposure via fugitive dust inhalation and soil and food ingestion; root uptake was the primary exposure route evaluated for vegetation. Total doses were compared with acceptable dose levels of 1.0 and 0.1 rad/day for vegetation and wildlife, respectively, with potentially unacceptable risks indicated for doses exceeding these levels. All estimated doses were below or approximated acceptable levels, typically by an order of magnitude or more. These results indicate that current levels of DU in soils do not pose unacceptable radiological risks to biota at the sites evaluated.     

Risk Assessment of Tropospheric Ozone: Human Health,Natural Resources,and Ecology

Ozone is an unusual trace gas in the atmosphere, presenting a challenge for risk assessors and risk managers. The challenge can be traced to the gas’ complex chemistry in the atmosphere (exposure), toxicology in biological systems (response), and the fledgling enterprise of risk assessment for widely distributed, highly reactive pollutants. This paper addresses the (i) co-evolution of the scientific data underlying ozone risk assessment on human health, natural resources (crops and managed forests), and unmanaged ecosystems, (ii) similarities and differences in risk assessment among these receptors, and (iii) utility of indicators in risk assessment. The scientific community has developed a sound database to underpin the ozone risk assessment, although the breadth and depth differ markedly among the three receptors. There are similarities in ozone risk assessment among human health, natural resources, and ecology, including features of exposure (e.g., temporal variation), response of plants and humans (e.g., sensitive cohorts), and integration of exposure and response (e.g., importance of peak and cumulative exposures). Equally important are the notable differences, and the more prominent are scaling of exposure-response relationships, air quality monitoring, economic valuation, and models to complement more traditional experimental approaches. Of the three receptors, the status of indicators for conducting ecological ozone risk assessment is the weakest.     

Health Risk Assessment of Chemical Mixtures Exposure to Residents in the Lake Taihu Region,China

This study assessed the mixture health risk for the residents of China's Lake Taihu region posed by a Persistent Organic Pollutants (POPs) mixture of dichloro-diphenyl-trichloroethane (DDT) and hexachlorocyclohexane (HCH). Multiple-pathway exposure models were used for exposure assessment in order to estimate the DDT and HCH exposure dose. The DDT and HCH PBPK models were developed and used for consequence assessment in order to analyze the pollutant distribution and accumulation process in human tissues. The tissue dose hazard index (HI) was used to estimate the mixture health risk. The results showed that the total exposure doses for male residents and female residents were 4.01 × 10^{? 4}～ 7.67 × 10^{? 3} mg/kg/day and 3.73 × 10^{? 4}～ 6.75 × 10^{? 3} mg/kg/day for DDT, respectively, and 3.78 × 10^{? 4}～ 5.14 × 10^{? 3} mg/kg/day and 3.53 × 10^{? 4}～ 4.66 × 10^{? 3} mg/kg/day for HCH, respectively. The maximum tissue concentrations in fat for male and female residents reached 110.51 mg/l and 97.21 mg/l for DDT, respectively, and 189.66 mg/l and 171.72 mg/l for HCH, respectively. The tissue dose hazard indexes for male and female residents were 0.1472 ～ 2.4990 and 0.1377 ～ 2.2230, respectively, and the probabilities of the risk exceeding the acceptable risk (HI = 1) for male and female were 24.60% and 16.51%, respectively.     

High-Throughput Exposure Assessment Tool (HEAT) for exposure-based prioritization of chemicals

Abstract

High-throughput methods are now routinely used to rapidly screen chemicals for potential hazard. However, hazard-based decision-making excludes important exposure considerations resulting in an incomplete estimation of chemical safety. Models to estimate exposure exist, but are generally unsuited to keep up with high-throughput demands. The High-Throughput Exposure Assessment Tool (HEAT) is designed to efficiently predict near-field exposure to consumers and workers via inhalation, oral and dermal routes. HEAT is based on well-known modeling algorithms and provides default model parameters to support reasonably conservative exposure estimates. Underlying chemical-specific data are uploaded or entered by the end user. HEAT’s main strength is the flexible tiered screening functionality, which enables exposure estimates for single or multiple chemicals simultaneously. Hypothetical case examples highlighting the application of HEAT to more complex exposure estimates for alternative and aggregate assessments are provided.     

A Probabilistic Human Health Risk Assessment for Environmental Exposure to Dibutylphthalate

In the European Union, Directive 92/32/EC and EC Council Regulation (EC) 793/93 require the risk assessment of industrial chemicals. In this framework, it is agreed to characterise the level of “risk” by means of the deterministic quotient of exposure and effects parameters. Decision makers require that the uncertainty in the risk assessment be accounted for as explicitly as possible. Therefore, this paper intends to show the advantages and possibilities of a probabilistic human health risk assessment of an industrial chemical, dibutylphthalate (DBP). The risk assessment is based on non-cancer endpoints assumed to have a threshold for toxicity. This example risk assessment shows that a probabilistic risk assessment in the EU framework covering both the exposure and the effects assessment is feasible with currently available techniques. It shows the possibility of comparing the various uncertainties involved in a typical risk assessment, including the uncertainty in the exposure estimate, the uncertainty in the effect parameter, and the uncertainty in assessment factors used in the extrapolation from experimental animals to sensitive human beings. The analysis done did not confirm the reasonable worst-case character of the deterministic EU-assessment of DBP. Sensitivity analysis revealed the extrapolation procedure in the human effects assessment to be the main source of uncertainty. Since the probabilistic approach allows determination of the range of possible outcomes and their likelihood, it better informs both risk assessors and risk managers.     

A Probabilistic Assessment of Household Exposures to MTBE from Drinking Water

The oxygenate methyl tertiary butyl ether (MTBE) has been added to reformulated gasoline in the U.S. to meet national ambient air quality standards. Although MTBE has provided significant health benefits in terms of reduced criteria and toxic air pollutants, detections of MTBE in some groundwater and drinking water sources have raised concerns about potential environmental contamination and human exposures. In this paper, we examine the frequency and concentration of MTBE detections in drinking water sources in California from 1995 to 1999, and provide a preliminary analysis of the distribution of household exposures to MTBE from water-related activities. Using published data on the toxicity and possible cancer hazard posed by MTBE, we estimate the likely cancer and non-cancer risks for the general population in California from past and potential future MTBE exposures. More highly exposed subgroups were also addressed. Our findings indicate that less than 2% of all sampled drinking water sources in California had detectable levels of MTBE in 1999, with average MTBE drinking water concentrations ranging from 0.09 to 4.9?ppb for this year. Both the detection rate for MTBE and average MTBE concentrations have remained relatively stable since 1995, despite increased sampling of drinking water sources in California. The probabilistic exposure analysis suggests that drinking water exposures to MTBE are unlikely to pose a significant health risk for the general population or more highly exposed individuals in California.     

Analysis and Portrayal of Uncertainty in a Food-Web Exposure Model

The results of quantitative risk assessments are key factors in a risk manager's decision of the necessity to implement actions to reduce risk. The extent of the uncertainty in the assessment will play a large part in the degree of confidence a risk manager has in the reported significance and probability of a given risk. The two main sources of uncertainty in such risk assessments are variability and incertitude. In this paper we use two methods, a second-order two-dimensional Monte Carlo analysis and probability bounds analysis, to investigate the impact of both types of uncertainty on the results of a food-web exposure model. We demonstrate how the full extent of uncertainty in a risk estimate can be fully portrayed in a way that is useful to risk managers. We show that probability bounds analysis is a useful tool for identifying the parameters that contribute the most to uncertainty in a risk estimate and how it can be used to complement established practices in risk assessment. We conclude by promoting the use of probability analysis in conjunction with Monte Carlo analyses as a method for checking how plausible Monte Carlo results are in the full context of uncertainty.     

The Ethical Conduct of Studies Involving Controlled Human Exposure to Environmental Pollutants

In recent years, the concern for human research subject protection has increased markedly in the United States. The nature of research subject participation in controlled-exposure environmental health research is such that the individual subject bears the risk of participation, while the benefits of such research accrue to society. Therefore, particular attention must be paid when designing studies to protect the health and safety of human research subject. This paper outlines principles for the appropriate selection of pollutants to which humans can be exposed, and the principles that should be used to protect the health and safety of human research subject.     

Exposure to Crystalline Silica Inhalation Among Construction Workers: A Probabilistic Risk Analysis

Crystalline silica and its presence in dust generated during various construction activities may pose a health hazard to construction workers. In this article, the occupational exposure to crystalline silica and the related long-term health (cancer and non-cancer) risks among construction workers from five different trades (activities) were evaluated using a probabilistic approach. The predicted 95th percentile of the excess lifetime cancer risk and hazard quotients for exposure to crystalline silica ranged from 4.5 × 10^?5 to 1.2 × 10^?4, and 15 to 37, respectively. The efficiency of the state-of-the-art technologies to reduce silica inhalation at construction sites are evaluated in the context of reduction in long-term health risks to the construction workers. The use of engineering controls and personal protective equipments to reduce the exposure to crystalline silica reduced the hazard quotient and excess lifetime cancer risk approximately by 65% and 78%, respectively. The sensitivity analyses showed that the exposure concentration of crystalline silica was the most significant parameter in both cancer and non-cancer risk estimates for the construction workers. The breathing rate, the exposure factor, and the daily shift hours also significantly contribute to the cancer and non-cancer risk estimates for the construction workers.     

Health Risk Assessment and Vapor Intrusion: A Review and Australian Perspective

Soil contamination by volatile hydrocarbons is of public health importance due to vapor intrusion and indoor inhalation exposures. These are assessed using measurement or predictive modeling and need to consider the key areas of subsurface partitioning and transport, dwelling ventilation, and receptor inhalation dosimetry. While subsurface partitioning and transport have been subject to intensive international investigation, limited consideration has been given to the latter. Building ventilation research has developed multi-zone airflow and contaminant dispersal models including AccuRate, an Australian model that examines natural ventilation modeling, roof and sub-floor ventilation, and identifies the importance of geometry and thermal factors on ventilation (the most sensitive variable) and indoor pollutant concentrations. Inhalation dosimetry has received recent attention due to concerns over child inhalation susceptibility and dose metrics. Research using coupled computational fluid dynamics (CFD) and physiologically based pharmaco-kinetic (PBPK) models has reported variance from previous animal models’ extrapolation while CFD modeling of transient lung vapor absorption suggests the significance of transient versus steady-state evaluation of volatiles absorption into tissue and blood. The transient nature of sub-surface fate and transport, ventilation, and inhalation uptake thus warrants integrated exploration and application in order to realize improvements in vapor intrusion assessments. These perspectives and Australian modeling initiatives are presented in this article.     

The Contribution of Systematic Review and Meta-Analysis Methods to Human Health Risk Assessment: Neurobehavioral Effects of Manganese

Current methods of human health risk assessment may lack transparency in respect of identification, review, and synthesis of potentially relevant human and animal evidence. The nature, degree, and source of uncertainties are often unclear. This article aims to demonstrate the contribution that systematic review and meta-analysis methods can make to providing more structured, transparent, and systematic risk assessments. We focus on disparities between five risk assessments for neurobehavioral effects of manganese, and then illustrate advantages of a systematic approach. Fifty-five human epidemiological studies and 37 animal experiments were identified. Where appropriate, meta-analysis methods demonstrated consistent adverse effects associated with manganese exposure across species. In particular, there was reduced activity in subjects exposed to manganese, although exposed rats tended to be more active than controls. Limitations of exposure measurement and reporting restricted use of more quantitative methods of evidence synthesis. From a methodological viewpoint, we conclude that systematic review and meta-analysis methods can contribute to a more systematic and transparent human health risk assessment making more efficient use of available evidence, compared to current methods of risk assessment. More complex methods could encompass further differences between relevant studies and so further improve the risk assessment process.     

The Importance of Human Data in the Establishment of Occupational Exposure Limits

The use of animal vs. human data for the purposes of establishing human risk was examined for four pharmaceutical compounds: acetylsalicylic acid, cyclophosphamide, indomethacin and clofibric acid. Literature searches were conducted to identify preclinical and clinical data useful for the derivation of acceptable daily intakes (ADIs) from which a number of risk values including occupational exposure limits (OELs) could be calculated. OELs were calculated using human data and then again using animal data exclusively. For two compounds, ASA and clofibric acid use of animal data alone led to higher OELs (not health protective), while for indomethacin and cyclophosphamide use of animal data resulted in the same or lower OELs based on human data alone. In each case arguments were made for why the use of human data was preferred. The results of the analysis support a basic principle of risk assessment that all available data be considered     

Combined Use of Life Cycle Assessment and Groundwater Transport Modeling to Support Contaminated Site Management

The subject of this study is a spent pot lining (SPL) landfill. The aim of this study was to identify the site remediation option, among four alternatives, that minimizes overall environmental impacts based on: 1) a comparative life cycle assessment (LCA); and 2) modeling of contaminant transport in groundwater. The four options were: leaving the landfill in place (Option 1); excavation of the landfill, with on-site disposal of the excavated materials in a secure cell (Option 2); excavation of the landfill, with treatment of the SPL fraction (Option 3); and excavation of the landfill, with incineration of the SPL fraction in a cement kiln (Option 4). The LCA was performed following the guidelines provided by the International Standard Organization (ISO). Furthermore, to improve the relevance of LCA to site remediation sector, impacts caused by residual in-situ contamination were assessed by applying a simulation of contaminant transport in groundwater, using site-specific data. The LCA identified Option 1 as having the least environmental impacts. However, the transport modeling concluded that contaminant concentrations 50 years from the present could be approximately 30 to 40 times the regulatory criteria if this option is retained. In addition, this study demonstrated that LCA can be used as a screening tool to help identify significant environmental issues; the LCA identified acute and chronic water ecotoxicity categories as being the dominant impact categories of the environmental profile and consequently, it is recommended that a complete environmental risk assessment (ERA) be performed for Option 1.     

Integration of the Predictions of Two Models with Dose Measurements in a Case Study of Children Exposed to the Emissions from a Lead Smelter

The predictions of two source-to-dose models are evaluated with observed data collected in a village polluted by an operating secondary lead smelter. Both models were built up from several sub-models linked together and run using Monte-Carlo simulation. The first model system provides the distribution of the media-specific lead concentrations (air, soil, fruit, vegetables, and blood) in the whole area investigated. The second model provides an estimate of the concentration of exposure of specific individuals living in the study area. The predictions of the first model system were improved by performing a sensitivity analysis and using field data to correct the default value provided for the leaf wet density. However, in this case study, the model system tends to overestimate the exposure due to exposed vegetables. The second model was tested for nine children with contrasting exposure conditions. It managed to capture the blood levels for eight of them. In the last case, the exposure of the child by pathways not considered in the model may explain the failure of the model. The interest of this integrated model is to provide outputs with lower variance than the first model system, but further tests are necessary to conclude about its accuracy.     

Health Risk Assessment of Petrol Station Workers in the Inner City of Bangkok,Thailand, to the Exposure to BTEX and Carbonyl Compounds by Inhalation

The occupational health risk of petrol station workers from exposure to BTEX and carbonyl compounds via inhalation was estimated in the inner city of Bangkok. Personal sampling was performed within the workers’ breathing zone using 2,4 dinitrophenylhydrazine cartridges and charcoal glass tubes connected to a personal air pump during eight working hours at six petrol stations. BTEX and carbonyl compounds were quantitatively analyzed by GC/FID and HPLC/UV, respectively. Of all detectable BTEX and carbonyl compounds, the levels of the four most prevalent compounds (benzene, ethylbenzene, formaldehyde, and acetaldehyde) were used to assess the lifetime cancer risk and 95% confidence interval of the risk levels were found to be totally higher than acceptable criteria for benzene (1.82 × 10^–4–2.50 × 10^–4), formaldehyde (7.81 × 10^–6–1.04 × 10^–5), ethylbenzene (4.11 × 10^–6–5.52 × 10^–6), and acetaldehyde (1.39 × 10^–6–2.45 × 10^–6). Thus, petrol station workers in the inner city of Bangkok have a potentially high cancer risk through inhalation exposure. With respect to the noncarcinogenic agents, toluene, m,p-xylene, o-xylene, and propionaldehyde, all non-cancer health risk were within hazard quotients of 1 and of acceptable risk.     

Evaluation of the Variation in Calculated Human Exposure to Soil Contaminants Using Seven Different European Models

Calculations using seven European exposure models were performed for 20 different exposure scenarios. The objective of this article is to understand the variation in the resulting calculated human exposures due to soil contamination. To this purpose, the variation in calculated exposures has been compared with the variation in calculated concentrations in contact media and in the soil compartments and with the variation in the input parameters. This led to the conclusion that most of the variation in Exposure through soil ingestion is explained by differences in the input parameter average daily soil intake. When model-specific input parameters are used the variation in Exposure through crop consumption is explained by differences in the product of total consumption rate and fraction of total consumption rate that is home-grown. When standardized input parameters are used, this variation is comparable with the variation in Concentration in root vegetables and in Concentration in leafy vegetables. The variation in Exposure through indoor air inhalation is comparable with the variation in Concentration in indoor air. This suggests that the parameters that control the variation in Concentration in the indoor air, that is, surface and volume of the building and, to a lesser extent, ventilation frequency of the building, also control the variation in Exposure through indoor air inhalation.