Exposure Assessment of Pharmaceuticals and Their Metabolites in the Aquatic Environment: Application to the French Situation and Preliminary Prioritization

Low levels of pharmaceuticals have been detected in many countries in surface waters. As a wide range of pharmaceuticals can reach aquatic environments, a selection of molecules to survey is the first step before implementing a monitoring program. We used a simple equation to calculate Predicted Environmental Concentrations (PECs), adapted from the European Medicine Agency model used for the Environmental Risk Assessment (ERA) of human pharmaceutical. Excretion fractions for pharmaceuticals were determined for 76 compounds. Using year 2004 French drug consumption data, we determined aquatic PECs for 112 parent molecules and several metabolites. Considering excretion fractions of pharmaceuticals can lead to drastically reduce predicted concentrations reaching the aquatic environment and help to target environmentally relevant pharmaceuticals and metabolites. Calculated PECs using the described methodology are consistent with French field measurements. The simple model for calculating PECs can be used as a valuable estimation of the exposure. Risk quotient ratios were also calculated. Due to the lack of ecotoxicological data, the use of PEC/PNEC ratios is not enough informative to prioritize pharmaceuticals likely to pose a risk for surface waters. Alternative ways to prioritize risk to pharmaceuticals, combining PEC, pharmacological, and ecotoxicological data available from the literature, should be implemented.     

The Cumulative Risk to Human Health of Pharmaceuticals in New Jersey Surface Water

Surface water in New Jersey is used by many residential drinking water facilities. Like many water sources it is contaminated by upstream industrial and residential sources, including pharmaceutical residues. This research examines the concentrations of 18 pharmaceuticals in 30 New Jersey locations, their acceptable daily exposures (ADE), and potential drug–drug interactions (DDI). The surface water data was provided by the U.S. Geological Survey (USGS). ADEs for human health were set for each pharmaceutical in the study. The pharmaceuticals were evaluated for known adverse health interactions and their potential health impact. These factors were brought together using a cumulative hazard index (HI) risk assessment calculation to assess the overall risk of pharmaceuticals in NJ surface water to human health. When examining the potential for DDI in this assessment, the risk increased but not appreciably. The HI for the sample locations ranged from <0.00001 to 0.01 with the DDI adding less than 1.2× increase to the overall risk. The calculated risk of these mixtures was also increased to an extreme DDI of 7 times per interaction. A noticeable increase in the calculated risk was seen, but in no cases did it reach a level of concern.     

Human Health Risk Assessment: Required Reading

Over the past 30 years, risk assessment has developed into a scientific discipline. It is critical that the next generation of risk assessors understand the history of our field, and recognize the numerous successes and failures that have taken place. This short Perspective identifies and describes specific books, monographs, and reports that are required reading for any nascent risk assessor.     

An Ecological Risk Assessment of Phenol in the Aquatic Environment

A probabilistic ecological risk assessment of phenol was undertaken to determine the risks posed to biota as a result of phenol release to the Canadian environment. A three-tiered approach was used to estimate risks, with progressively more realistic assumptions being applied at each tier. In Canada, the major sources of phenol are municipal wastewater treatment plants, pulp, paper and wood products mills, steel and metal products facilities and refineries. Thus, the highest exposures will occur in receiving waters near these point sources, primarily due to the short half-life of phenol in the aquatic environment. Sensitive aquatic organisms include salmonids (e.g., rainbow trout Oncorhynchus mykiss) and amphibians (e.g., leopard frog Rana pipiens). The results of the risk assessment indicate that species are exposed to elevated levels of phenol near point sources, but these levels represent only a minor risk to aquatic biota.     

Framework for Human Health Risk Assessment

The views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the USEPA. The U.S. Government has the right to retain a nonexclusive royalty-free license in and to any copyright covering this article. The U.S. Environmental Protection Agency has recognized the need to develop a framework for human health risk assessment that puts a perspective on the approaches in practice throughout the Agency. In response, the USEPA's Risk Assessment Forum has begun the process of developing a framework for human health risk assessment. This paper provides some additional background to the previous review of the framework efforts and notes the Agency's extramural efforts to begin the process of integrating and harmonizing risk assessment approaches for all human health endpoints.     

An Ecological Risk Assessment of Ammonia in the Aquatic Environment

Ammonia is released in the environment by many industries and other human activities. The major quantifiable sources of ammonia released to aquatic ecosystems across Canada are municipal wastewater treatment plants, at an estimated total quantity of 62,000 tonnes per year. Given the sources of ammonia releases in the environment and the properties of the substance, terrestrial plants and aquatic organisms are potential risk targets. A tiered assessment approach has been used to determine the ecological risk in the aquatic environment from ammonia released in municipal wastewater effluents. The results obtained for two case studies with the probabilistic risk analysis used in the highest tier support the conclusion that the conditions encountered in these two locations can lead to ammonia concentrations capable of producing an adverse ecological impact.     

A Preliminary Human Health Risk Assessment of Organochlorine Pesticide Residues Associated with Aquatic Organisms from the Rangsit Agricultural Area,Central Thailand

Food consumption is one of the main routes of human exposure to organochlorine pesticide residues (OCPRs). To assess the potential health risks associated with OCPRs contaminants due to freshwater organism consumption, a number of vegetables, prawn, snail, and fish were collected from Khlong 7 (canal), Rangsit agricultural area, Pathum-Thani Province, Thailand. The samples were extracted using a multiresidue extraction method and then analyzed by gas chromatography with microelectron capture detector (μ -ECD). The results show that low concentrations of OCPRs were detected in parts per billion (ppb) levels. Based on a plausible worst-case scenario, the local population could be at risk for cancer due to consumption of fish contaminated by α -, β -HCH, heptachlor, heptachlor epoxide, aldrin, dieldrin, DDD, DDE, and DDT. Likewise, individuals may be at risk from consumption of Lanchester's freshwater prawn Macrobrachium lanchesteri, freshwater snail Filopaludina mertensi, swamp morning-glory Ipomomea aquatica, neptunia Neptunia oleracea, and water lily Nymphaea lotus because these species all contained elevated concentrations of α -, β -HCH, heptachlor, heptachlor epoxide, aldrin, and dieldrin.     

An Ecological Risk Assessment of Nonylphenol and Its Ethoxylates in the Aquatic Environment

Nonylphenol ethoxylates (NPEs) are a group of surfactants that are widely used for industrial, commercial, institutional and household purposes in Canada. Ethoxylation of nonylphenol (NP) occurs upon reaction with ethylene oxide, producing NPEs, although NP is also used in the production of the antioxidant tris(nonylphenol)phosphite. NP and NPEs are not produced naturally, and the primary route of environmental exposure to NP and NPEs is via textile mill, pulp and paper mill and municipal wastewater treatment plant effluents. NPEs occur as complex mixtures and are described by the average ethoxylate chain length, which ranges from 1 to 100. The environmental fate of NPEs is strongly dependent on the effluent and, the degree and type of treatment to which the effluent is subjected. An ecological risk assessment was performed to determine if exposure to NP and NPEs results in effects on the Canadian environment, based on current use patterns. The Canadian ecological risk assessment found that adverse effects on aquatic organisms are likely, although assumptions were made with respect to appropriate dilution factors.     

The Concept of Data Utility in Health Risk Assessment: A Multi-Disciplinary Perspective

Human and ecological health risk assessments and the decisions that stem from them require the acquisition and analysis of data. In agencies that are responsible for health risk decision-making, data (and/or opinions/judgments) are obtained from sources such as scientific literature, analytical and process measurements, expert elicitation, inspection findings, and public and private research institutions. Although the particulars of conducting health risk assessments of given disciplines may be dramatically different, a common concern is the subjective nature of judging data utility. Often risk assessors are limited to available data that may not be completely appropriate to address the question being asked. Data utility refers to the ability of available data to support a risk-based decision for a particular risk assessment. This article familiarizes the audience with the concept of data utility and is intended to raise the awareness of data collectors (e.g., researchers), risk assessors, and risk managers to data utility issues in health risk assessments so data collection and use will be improved. In order to emphasize the cross-cutting nature of data utility, the discussion has not been organized into a classical partitioning of risk assessment concerns as being either human health- or ecological health-oriented, as per the U.S. Environmental Protection Agency's Superfund Program.     

Human Health Risk Assessment at a Depleted Uranium Site

Human health risk assessments for depleted uranium are common for Department of Defense (DOD) sites since the metal has various military uses. At a training and experimental site, DU was evaluated in soil in order to make decisions regarding cleanup and future use of the site. At this site, concentrations were found to be protective of human health; DU is less toxic than uranium. Other data important to this decision were the type of receptors likely to be exposed, the amount of time spent by the receptor on-site, the acceptable yearly radiation dose, and other non-radiation associated effects to the kidney. Total uranium concentrations in soil were calculated for the 90th percentile and the 50th percentile. The highest soil concentration used as an exposure point was 3500 ug/g (90th percentile). Short exposure timeframes contributed to the risk results.     

Arsenic in Seafood: Speciation Issues for Human Health Risk Assessment

Major sources of arsenic exposure for humans are foods, particularly aquatic organisms, which are called seafood in this report. Although seafood contains a variety of arsenicals, including inorganic arsenic, which is toxic and carcinogenic, and arsenobetaine, which is considered nontoxic, the arsenic content of seafood commonly is reported only as total arsenic. A goal of this literature survey is to determine if generalizable values can be derived for the percentage of total arsenic in seafood that is inorganic arsenic. Generalizable values for percent inorganic arsenic are needed for use as default values in U.S. human health risk assessments of seafood from arsenic-contaminated sites. Data from the worldwide literature indicate the percent of inorganic arsenic in marine/estuarine finfish does not exceed 7.3% and in shellfish can reach 25% in organisms from presumably uncontaminated areas, with few data available for freshwater organisms. However, percentages can be much higher in organisms from contaminated areas and in seaweed. U.S. site-specific data for marine/estuarine finfish and shellfish are similar to the worldwide data, and for freshwater finfish indicate that the average percent inorganic arsenic is generally < 10%, but ranges up to nearly 30%. Derivation of nationwide defaults for percent inorganic arsenic in fish, shellfish, and seaweed collected from arsenic-contaminated areas in the United States is not supported by the surveyed literature.     

An Assessment of Integrated Risk Assessment

In order to promote international understanding and acceptance of the integrated risk assessment process, the World Health Organization/International Programme on Chemical Safety (WHO/IPCS), in collaboration with the U.S. Environmental Protection Agency and the Organization for Economic Cooperation and Development, initiated a number of activities related to integrated risk assessment. In this project, the WHO/IPCS defines integrated risk assessment as a science-based approach that combines the processes of risk estimation for humans, biota, and natural resources in one assessment. This article explores the strengths and weaknesses of integration as identified up to this date and the degree of acceptance of this concept by the global risk assessment/risk management community. It discusses both opportunities and impediments for further development and implementation.

The major emerging opportunities for an integrated approach stem from the increasing societal and political pressure to move away from vertebrate testing leading to a demand for scientific integrated approaches to in vitro and in vivo testing, as well as to computer simulations, in so-called Intelligent Testing Strategies. In addition, by weighing the evidence from conventional mammalian toxicology, ecotoxicology, human epidemiology, and eco-epidemiology, risk assessors could better characterize mechanisms of action and the forms of the relationships of exposures to responses. It is concluded that further demonstrations of scientific, economic and regulatory benefits of an integrated approach are needed. As risk assessment is becoming more mechanistic and molecular this may create an integrated approach based on common mechanisms and a common systems-biology approach.     

Human Health Risk Assessment of Non-Regulated Xenobiotics in Recycled Water: A Review

Water suppliers face increased pressure to explain the relative health risks from non-regulated xenobiotics that may be present in recycled water, including pharmaceuticals and personal care products (PPCPs) and endocrine disrupting compounds. This report reviews their occurrence, fate, and recent human health risk assessments for potable and non-potable water reuse. The most effective advanced treatment for PPCPs is reverse osmosis (RO) followed by advanced oxidation. During soil aquifer treatment, the majority of PPCPs are attenuated relatively quickly (within 100 days), yet some are persistent and can migrate to the underlying groundwater at low concentrations. Recently, several investigations have assessed the potential human health risks associated with xenobiotics in recycled water, focusing on exposure from drinking water (e.g., planned and unplanned indirect potable reuse) and non-potable reuse (e.g., exposure via recreational, occupational, and irrigation-related activities at sites utilizing recycled water). Risk assessments conducted over the last 10 years have found no adverse human health effects or significant risks. Though advanced treatment of wastewater that is discharged or recycled may not be required to protect public health, it may be necessary to prevent potential effects on exposed biota and to address, to some degree, the public's perception of water reuse.     

Human Health Risk Assessment of a Civilian-Accessible Active Firing Range

The Korean Federation of Teachers Association, the Korea Ministry of Education, Science and Technology, and the Korea Ministry of National Defense (KMND) concluded a memorandum of understanding (MOU) on opening military sites to elementary, middle, and high school students to strengthen national security consciousness. According to the MOU, the KMND decided to open an active firing range; however, due to the ongoing firing activity, site contamination by toxic energetic materials (EMs) was suspected. To identify whether opening the firing range might pose a human health threat to the students and their teachers visiting the site, we conducted a risk assessment to evaluate potential risk. The risk assessment results revealed that both cancer risk and non-cancer risk were negligible. The potential cancer risk was in the range of 1.9 × 10^–11 and 1.4 × 10^–10, and the potential non-cancer hazard index was in the range of 2.3 × 10^–6 and 4.9 × 10^–6.     

Recent Developments in Nanotechnology and Risk Assessment Strategies for Addressing Public and Environmental Health Concerns

Nanotechnology is a novel emerging technology that allows the manipulation of materials at the scale comparable to the size of a single molecule (i.e., < 100 nm). There have been many new developments in this technology, resulting in complex exposure and health risk implications. Nanotechnology offers major benefits to humankind; however, there is growing concern regarding the potential adverse interactions of engineered nanoparticles at cellular or sub-cellular levels. The nanotech community is therefore experiencing growing calls for legislation to minimize or prevent exposure to nanoparticles. This article focuses on recent developments in nanotechnology including current manufacturing techniques, uses of nanoscale particles, and implications for particle toxicity and human exposure pathways. Current risk assessment methods are reviewed in the context of nanoparticle exposure routes and regulation for human and environmental health protection. This study provides a better understanding of the factors governing risks from nanoparticles and current strategies for protecting environmental and public health.     

Human Health Risks of Selenium-Contaminated Fish: A Case Study for Risk Assessment of Essential Elements

A screening level human health risk assessment (HHRA) was applied to evaluate the human health implications of consuming selenium found in fish tissues collected downstream of coal mines in southeastern British Columbia, Canada. The study evaluated the potential for adverse human health effects associated with selenium, and considered known and potential benefits of selenium and fish ingestion. The results indicated that risks of selenosis due to consumption of selenium-contaminated fish in the region are negligible. Conclusions were strengthened by consideration of the potential benefits of selenium to human health, including: selenium essentiality for maintenance of good health; potential cancer prevention properties due to its role as an antioxidant; potential benefits for cardiovascular health; and other positive health benefits. The findings indicated that some aspects of the traditional framework for HHRA (e.g., application of safety factors to “err on the side of safety”) are inappropriate for the assessment of selenium-contaminated fish. Due to both deficiency and toxicity in the selenium dose-response relationship, application of compounding conservatism in risk assessment may lead to recommended intakes of fish that are contrary to the public health interest. The need for balancing risk types, for incorporating positive responses in risk assessments, and the linkage to the precautionary principle, are discussed.     

Aquatic Risk Assessment of Metals in Sediment from South Florida Canals

A major watershed restoration effort is underway in south Florida, yet there are significant gaps in scientific information on exposure and risks of contaminants to its natural resources. We conducted a two-tier aquatic screening-level ecological risk assessment for metals that were monitored in sediment at 32 sampling sites in south Florida freshwater canals from 1990–2002. For tier 1, the chemicals (or metals) of potential ecological concern (COPECs) were identified as arsenic, cadmium, chromium, copper, lead, nickel and zinc based on their exceedences of Florida sediment quality guidelines at 10 sites. For tier 2, we used a probabilistic risk assessment method to compare distributions of predicted pore water exposure concentrations of seven metal COPECs with distributions of species response data from laboratory toxicity tests to quantify the likelihood of risk. The overlap of pore water concentrations (90th centile for exposure) for metal COPECs and the effects distributions for arthropods (10th centile of LC50s) and all species (10th centile of chronic NOECs) were used as a measure of potential acute and chronic risks, respectively. Arsenic (25%) in the Holey Land tracts, in Broward County north of Everglades National Park (ENP), and chromium (25%) in the C-111 freshwater system, at the east boundary of ENP, were the most frequently detected COPECs in sediment. Antimony (6%), zinc (6%) and lead (5%) were the least frequently detected COPECs in sediment. The 90th centile concentrations for bulk sediment were highest for zinc (at S-178) and lead (at S-176) in the C-111system. The 90th centile concentration for pore water exposure was highest for arsenic in the Holey Land tracts and lowest for cadmium and chromium. The estimated acute 10th centile concentration for effects was lowest for copper and arthropods. The probabilities of pore water exposures of copper exceeding the estimated acute 10th centile concentration from the species sensitivity distributions (SSD) of acute toxicity data (for arthropods) were 57 and 100% for copper at S-177 and S-178 in the C-111 system, respectively. The probability of pore water exposures of copper exceeding the estimated NOEC 10th centile concentration from the SSD of chronic toxicity data (for all species) was 93 and 100% for copper at S-177 and S-178, respectively. Uncertainties in exposure and effects analysis and risk characterization are identified and discussed. The study presents a straightforward approach to estimate exposure and potential risks of metals detected in sediment from south Florida canals.     

Framework for the Integration of Health and Ecological Risk Assessment

The World Health Organization's International Programme on Chemical Safety (IPCS), the Organization for Economic Cooperation and Development (OECD), and the U.S. Environmental Protection Agency have developed a collaborative partnership to foster integration of assessment approaches for human health and ecological risks. This paper presents the framework developed by that group. Integration provides coherent expressions of assessment results, incorporates the interdependence of humans and the environment, uses sentinel organisms, and improves the efficiency and quality of assessments relative to independent human health and ecological risk assessments. The paper describes how integration can occur within each component of risk assessment, and communicates the benefits of integration at each point. The goal of this effort is to promote the use of this internationally accepted guidance as a basis for harmonization of risk assessment.     

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.