Are current tissue-based selenium guidelines and criteria overly protective of freshwater fish populations? A critical review with recommendations.

Several decades after selenium impacts on wild fish populations were observed in freshwater reservoirs receiving fly ash effluents from electric power facilities at Belews Lake and Hyco Reservoir (North Carolina, USA), developments in selenium (Se) toxicology have led to a greater understanding of Se effects on freshwater fish. These latter advancements have allowed regulatory agencies in several jurisdictions to develop tissue-based toxicity benchmarks for the protection of aquatic life. These benchmarks were generally derived from datasets encompassing multiple fish species and designed to protect the most sensitive species (US Environmental Protection Agency [EPA] water quality criteria). Safety factors have been applied in the development of some Canadian guidelines (British Columbia [BC]), resulting in guidelines that appear to be overly conservative. The present study addresses the question, "Are current tissue-based selenium guidelines and criteria overly protective of freshwater fish populations?" A literature review was conducted of studies in which Se was the primary constituent of concern, to compare tissue concentrations and results of fish population metrics and deformity assessment studies with current regulatory thresholds for the protection of aquatic life in the United States and Canada. EPA fish tissue-based Se criteria were found to be protective of fish populations and, at times, overly protective. Canadian water quality guidelines for Se (BC Ministry of Environment and Climate Change Strategy [BCMOECCS], Environment and Climate Change Canada [ECCC]) were consistently found to be overly protective, especially for benchmarks in which safety factors were used to derive those guidelines. In addition to a synthesis of the results of these studies, various limitations of the reviewed studies are discussed, and recommendations for future studies are proposed. Integr Environ Assess Manag 2022;18:622-630. © 2021 SETAC.

Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper.

Decades of study indicate that copper oral exposures are typically not a human health concern. Ingesting high levels of soluble copper salts can cause acute gastrointestinal symptoms and, in uncommon cases, liver toxicity in susceptible individuals with repeated exposure. This focused toxicological review evaluated the current literature since the last comprehensive reviews (2007-2010). Our review identified limitations in the existing United States and international guidance for determining an oral reference dose (RfD) for essential metals like copper. Instead, an alternative method using categorical regression analysis to develop an optimal dose that considers deficiency, toxicity, and integrates information from human and animal studies was reviewed for interpreting an oral RfD for copper. We also considered subchronic or chronic toxicity from genetic susceptibility to copper dysregulation leading to rare occurrences of liver and other organ toxicity with elevated copper exposure. Based on this approach, an oral RfD of 0.04 mg Cu/kg/day would be protective of acute or chronic toxicity in adults and children. This RfD is also protective for possible genetic susceptibility to elevated copper exposure and allows for background dietary exposures. This dose is not intended to be protective of patients with rare genetic disorders for copper sensitivity within typical nutritional intake ranges, nor is it protective for those with excessive supplement intake. Less soluble mineral forms of copper in soil have reduced bioavailability as compared with more soluble copper in water and diet, which should be considered in using this RfD for risk assessments of copper.

Use of Multiple Linear Regression Models for Setting Water Quality Criteria for Copper: A Complementary Approach to the Biotic Ligand Model.

Biotic Ligand Models (BLMs) for metals are widely applied in ecological risk assessments and in the development of regulatory water quality guidelines in Europe, and in 2007 the United States Environmental Protection Agency (USEPA) recommended BLM-based water quality criteria (WQC) for Cu in freshwater. However, to-date, few states have adopted BLM-based Cu criteria into their water quality standards on a state-wide basis, which appears to be due to the perception that the BLM is too complicated or requires too many input variables. Using the mechanistic BLM framework to first identify key water chemistry parameters that influence Cu bioavailability, namely dissolved organic carbon (DOC), pH, and hardness, we developed Cu criteria using the same basic methodology used by the USEPA to derive hardness-based criteria but with the addition of DOC and pH. As an initial proof of concept, we developed stepwise multiple linear regression (MLR) models for species that have been tested over wide ranges of DOC, pH, and hardness conditions. These models predicted acute Cu toxicity values that were within a factor of ±2 in 77% to 97% of tests (5 species had adequate data) and chronic Cu toxicity values that were within a factor of ±2 in 92% of tests (1 species had adequate data). This level of accuracy is comparable to the BLM. Following USEPA guidelines for WQC development, the species data were then combined to develop a linear model with pooled slopes for each independent parameter (i.e., DOC, pH, and hardness) and species-specific intercepts using Analysis of Covariance. The pooled MLR and BLM models predicted species-specific toxicity with similar precision; adjusted R2 and R2 values ranged from 0.56 to 0.86 and 0.66-0.85, respectively. Graphical exploration of relationships between predicted and observed toxicity, residuals and observed toxicity, and residuals and concentrations of key input parameters revealed many similarities and a few key distinctions between the performances of the two models. The pooled MLR model was then applied to the species sensitivity distribution to derive acute and chronic criteria equations similar in form to the USEPA's current hardness-based criteria equations but with DOC, pH, and hardness as the independent variables. Overall, the MLR is less responsive to DOC than the BLM across a range of hardness and pH conditions but more responsive to hardness than the BLM. Additionally, at low and intermediate hardness, the MLR model is less responsive than the BLM to pH, but the two models respond comparably at high hardness. The net effect of these different response profiles is that under many typical water quality conditions, MLR- and BLM-based criteria are quite comparable. Indeed, conditions where the two models differ most (high pH/low hardness and low pH/high hardness) are relatively rare in natural aquatic systems. We suggest that this MLR-based approach, which includes the mechanistic foundation of the BLM but is also consistent with widely accepted hardness-dependent WQC in terms of development and form, may facilitate adoption of updated state-wide Cu criteria that more accurately account for the parameters influencing Cu bioavailability than current hardness-based criteria.

Effect of Fe (III) on Pseudokirchneriella subcapitata at circumneutral pH in standard laboratory tests is explained by nutrient sequestration.

The complex chemistry of iron (Fe) at circumneutral pH in oxygenated waters and the poor correlation between ecotoxicity results in laboratory and natural waters have led to regulatory approaches for iron based on field studies (US Environmental Protection Agency Water Quality Criteria and European Union Water Framework Directive proposal for Fe). The results of the present study account for the observed differences between laboratory and field observations for Fe toxicity to algae (Pseudokirchneriella subcapitata). Results from standard 72-h assays with Fe at pH 6.3 and pH 8 resulted in similar toxicity values measured as algal biomass, with 50% effect concentrations (EC50) of 3.28 mg/L and 4.95 mg/L total Fe(III), respectively. At the end of the 72-h exposure, however, dissolved Fe concentrations were lower than 30 µg/L for all test concentrations, making a direct toxic effect of dissolved iron on algae unlikely. Analysis of nutrient concentrations in the artificial test media detected phosphorus depletion in a dose-dependent manner that correlated well with algal toxicity. Subsequent experiments adding excess phosphorus after Fe precipitation eliminated the toxicity. These results strongly suggest that observed Fe(III) toxicity on algae in laboratory conditions is a secondary effect of phosphorous depletion. Environ Toxicol Chem 2017;36:952-958. © 2016 SETAC.

Long-term monitoring of arsenic, copper, selenium, and other elements in Great Salt Lake (Utah, USA) surface water, brine shrimp, and brine flies.

This paper presents long-term monitoring data for 19 elements with a focus on arsenic (As), copper (Cu), and selenium (Se), in surface water (2002-2011), brine shrimp (2001-2011), and brine flies (1995-1996) collected from Great Salt Lake (GSL, Utah, USA). In open surface waters, mean (±standard deviation [SD]; range; n) As concentrations were 112 (±22.1; 54.0-169; 47) and 112 µg/L (±35.6; 5.1-175; 68) in filtered and unfiltered surface water samples, respectively, and 16.3 µg/g (±5.6; 5.1-35.2; 62) dry weight (dw) in brine shrimp. Mean (±SD; range; n) Cu concentrations were 4.2 (±2.1; 1.3-12.5; 47) and 6.9 µg/L (±6.6; 1.9-38.1; 68) in filtered and unfiltered surface water samples, respectively, and 20.6 µg/g (±18.4; 5.4-126; 62) dw in brine shrimp. Finally, mean (±SD; range; n) dissolved and total recoverable Se concentrations were 0.6 (±0.1; 0.4-1.2; 61) and 0.9 µg/L (±0.7; 0.5-3.6; 89), respectively, and 3.6 µg/g (±2.2; 1.1-14.9; 98) dw in brine shrimp. Thus, Se in open lake surface waters was most often in the range of 0.5-1 µg/L, and concentrations in both surface water and brine shrimp were comparable to concentrations measured in other monitoring programs for the GSL. Temporally, the statistical significance of differences in mean dissolved or total recoverable As, Cu, and Se concentrations between years was highly variable depending which test statistic was used, and there was no clear evidence of increasing or decreasing trends. In brine shrimp, significant differences in annual mean concentrations of As, Cu, and Se were observed using both parametric and nonparametric statistical approaches, but, as for water, there did not appear to be a consistent increase or decrease in concentrations of these elements over time.

Predictive modeling of selenium accumulation in brine shrimp in saline environments.

Great Salt Lake, Utah, is a large, terminal, hypersaline lake consisting of a northern more saline arm and a southern arm that is less saline. The southern arm supports a seasonally abundant fauna of low diversity consisting of brine shrimp (Artemia franciscana), 7 species of brine flies, and multiple species of algae. Although fish cannot survive in the main body of the lake, the lake is highly productive, and brine shrimp and brine fly populations support large numbers of migratory waterfowl and shorebirds, as well as resident waterfowl, shorebirds, and gulls. Selenium and other trace elements, metals, and nutrients are contaminants of concern for the lake because of their concentrations in municipal and industrial outfalls and runoff from local agriculture and the large urban area of Salt Lake City. As a consequence, the State of Utah recently recommended water quality standards for Se for the southern arm of Great Salt Lake based on exposure and risk to birds. The tissue-based recommendations (as measured in bird eggs) were based on the understanding that Se toxicity is predominately expressed through dietary exposure, and that the breeding shorebirds, waterfowl, and gulls of the lake are the receptors of most concern. The bird egg-based recommended standards for Se require a model to link bird egg Se concentrations to their dietary concentrations and water column values. This study analyzes available brine shrimp tissue Se data from a variety of sources, along with waterborne and water particulate (potential brine shrimp diet) Se concentrations, in an attempt to develop a model to predict brine shrimp Se concentrations from the Se concentrations in surrounding water. The model can serve as a tool for linking the tissue-based water quality standards of a key dietary item to waterborne concentrations. The results were compared to other laboratory and field-based models to predict brine shrimp tissue Se concentrations from ambient water and their diet. No significant relationships were found between brine shrimp and their dietary Se, as measured by seston concentrations. The final linear and piecewise regression models showed significant positive relationships between waterborne and brine shrimp tissue Se concentrations but with a very weak predictive ability for waterborne concentrations<10 µg/L.

What is an appropriate level of protection? An example considering selenium exposures by aquatic birds.

Evaluating population-level risks to ecological receptors or developing toxicity thresholds intended to be protective of a population requires a population model to truly understand possible chemical-related impacts to the population of interest. For various reasons (e.g., lack of training in the application of population models to ecotoxicological questions), we often use laboratory-based (more common) or field-based (less common) toxicity data to develop a toxicity threshold that is assumed to be protective of population-level effects. Under this latter approach, an appropriate level of protection against exposure should focus on protecting the viability and productivity of populations of organisms, that is, maintaining approximately the same density of individuals over time. The EC values can be used to set technically defensible levels of protection, with the appropriate effect level being determined on the basis of data- and site-specific considerations and dose-response relationships that are amenable for use as inputs in population models. Even without the use of predictive population models, the ECO10 or EC20 are commonly used values in risk assessment or criteria development with the assumption of adequate protection of populations. In the Se example presented here, there is strong evidence that egg hatchability is the critical toxicity endpoint for birds based on dietary organic Se exposures and that mallards are a sensitive bird species. These factors support that the dietary Se EC10 derived by Ohlendorf (2003) is sufficiently low to not have any measurable effects on aquatic birds in the field. Further, effect levels below the EC10 are likely to be statistically indistinguishable from the controls in most situations (as it was for Se in this example), and, for Se and other naturally occurring elements, it is not unusual for lower EC values to approach or fall below background levels at a site. A determination as to whether higher EC values would also provide an adequate level of protection could be made by appropriate population modeling.

Assessing metal bioaccumulation in aquatic environments: the inverse relationship between bioaccumulation factors, trophic transfer factors and exposure concentration.

Bioaccumulation potential in aquatic biota is typically expressed using ratios of chemical concentrations in organism tissue (typically whole body) relative to chemical exposure concentrations, such as bioconcentration factors (BCFs). Past reviews of metal BCFs for aquatic biota, which account for water-only exposures, have shown that BCFs are often highly variable between organisms and generally inversely related to exposure concentration. This paper further evaluates trends in metal bioaccumulation data by evaluating data for bioaccumulation factors (BAFs) and trophic transfer factors (TTFs). Bioaccumulation factor data were compiled from field studies that account for combined waterborne and dietary metal exposures. Trophic transfer factor data for metals were compiled from laboratory studies in which aquatic food chains were simulated. Natural aquatic food webs are rarely sufficiently understood to properly evaluate exact predator-prey relationships (i.e., TTFs). Results indicate that field BAFs, like laboratory BCFs, tend to be significantly (p < or = 0.05) inversely related to exposure concentration. Bioaccumulation factors are frequently 100-1000 times larger than BCFs for the same metal and species. This difference is attributed to both lower exposure levels in the field and inclusion of the dietary exposure route. Trophic transfer factors for the metals reviewed, including selenium and methyl mercury were also observed to be inversely related to exposure concentration, particularly at lower exposure concentrations. These inverse relationships have important implications for environmental regulations (e.g., hazard classification and tissue residue-based water quality criteria) and for the use of metal bioaccumulation data in site-specific environmental evaluations, such as ecological and human health risk assessments. Data presented indicate that for metals and metalloids, unlike organic substances, no one BAF or TTF can be used to express bioaccumulation and/or trophic transfer without consideration of the exposure concentration.

Setting site-specific water-quality standards by using tissue residue thresholds and bioaccumulation data. Part 2. Calculating site-specific selenium water-quality standards for protecting fish and birds.

In a companion paper, a method for deriving tissue residue-based site-specific water-quality standards (SSWQSs) was described. In this paper, the methodology is applied to selenium (Se) as an example. Models were developed to describe Se bioaccumulation in aquatic-dependent bird eggs and whole fish. A simple log-linear model best described Se accumulation in bird eggs (r2 = 0.50). For fish, separate hockey stick regressions were developed for lentic (r2 = 0.65) and lotic environments (r2 = 0.37). The low r2 value for the lotic fish model precludes its reliable use at this time. Corresponding tissue residue criteria (i.e., tissue thresholds) for bird eggs and whole fish also were identified and example model predictions were made. The models were able to predict SSWQSs over a wide range of water-tissue combinations that might be encountered in the environment. The models also were shown to be sensitive to variability in measured tissue residues with relatively small changes in variability (as characterized by the standard error) resulting in relatively large differences in SSWQSs.

Derivation of a chronic site-specific water quality standard for selenium in the Great Salt Lake, Utah, USA.

The purpose of this study was to develop a site-specific water quality standard for selenium in the Great Salt Lake, Utah, USA. The study examined the bioavailability and toxicity of selenium, as selenate, to biota resident to the Great Salt Lake and the potential for dietary selenium exposure to aquatic dependent birds that might consume resident biota. Because of its high salinity, the lake has limited biological diversity with bacteria, algae, diatoms, brine shrimp, and brine flies being the only organisms present in the main (hypersaline) portions of the lake. To evaluate their sensitivity to selenium, a series of acute and chronic toxicity studies were conducted on brine shrimp (Artemia franiciscana), brine fly (Ephydra cinerea), and a hypersaline alga (Dunaliella viridis). The resulting acute and chronic toxicity data indicated that resident species are more selenium tolerant than many freshwater species. Because sulfate is known to reduce selenate bioavailability, this selenium tolerance is thought to result in part from the lake's high ambient sulfate concentrations (>5,800 mg/L). The acute and chronic test results were compared to selenium concentrations expected to occur in a mining effluent discharge located at the south end of the lake. Based on these comparisons, no appreciable risks to resident aquatic biota were projected. Field and laboratory data collected on selenium bioaccumulation in brine shrimp demonstrated a linear relationship between water and tissue selenium concentrations. Applying a dietary selenium threshold of 5 mg/kg dry weight for aquatic birds to this relationship resulted in an estimate of 27 microg/L Se in water as a safe concentration for this exposure pathway and an appropriate chronic site-specific water quality standard. Consequently, protection of aquatic birds represents the driving factor in determining a site-specific water quality standard for selenium.

Analysis of field and laboratory data to derive selenium toxicity thresholds for birds.

In this paper, we critically evaluate the statistical approaches and datasets previously used to derive chronic egg selenium thresholds for mallard ducks (laboratory data) and black-necked stilts (field data). These effect concentration thresholds of 3%, 10% (EC10), or 20% have been used by regulatory agencies to set avian protection criteria and site remediation goals, thus the need for careful assessment of the data. The present review indicates that the stilt field dataset used to establish a frequently cited chronic avian egg selenium threshold of 6 mg/kg dry weight lacks statistical robustness (r2 = 0.19-0.28 based on generalized linear models), suggesting that stilt embryo sensitivity to selenium is highly variable or that factors other than selenium are principally responsible for the increase in effects observed at the lower range of this dataset. Hockey stick regressions used with the stilt field dataset improve the statistical relationship (r2 = 0.90-0.97) but result in considerably higher egg selenium thresholds (EC10 = 21-31 mg/kg dry wt). Laboratory-derived (for mallards) and field-derived (for stilts) teratogenicity EC10 values are quite similar (16-24 mg/kg dry wt). Laboratory data regarding mallard egg inviability and duckling mortality data provide the most sensitive and statistically robust chronic threshold (EC10) with logit, probit, and hockey stick regressions fitted to laboratory data, resulting in mean egg selenium EC10 values of 12 to 15 mg/kg dry weight (r2 = 0.75-0.90).