Bioavailability and Toxicity Models of Copper to Freshwater Life: The State of Regulatory Science

Abstract

Efforts to incorporate bioavailability adjustments into regulatory water quality criteria in the United States have included four major procedures: hardness-based single-linear regression equations, water-effect ratios (WERs), biotic ligand models (BLMs), and multiple-linear regression models (MLRs) that use dissolved organic carbon, hardness, and pH. The performance of each with copper (Cu) is evaluated, emphasizing the relative performance of hardness-based versus MLR-based criteria equations. The WER approach was shown to be inherently highly biased. The hardness-based model is in widest use, and the MLR approach is the US Environmental Protection Agency's (USEPA's) present recommended approach for developing aquatic life criteria for metals. The performance of criteria versions was evaluated with numerous toxicity datasets that were independent of those used to develop the MLR models, including olfactory and behavioral toxicity, and field and ecosystem studies. Within the range of water conditions used to develop the Cu MLR criteria equations, the MLR performed well in terms of predicting toxicity and protecting sensitive species and ecosystems. In soft waters, the MLR outperformed both the BLM and hardness models. In atypical waters with pH <5.5 or >9, neither the MLR nor BLM predictions were reliable, suggesting that site-specific testing would be needed to determine reliable Cu criteria for such settings. The hardness-based criteria performed poorly with all toxicity datasets, showing no or weak ability to predict observed toxicity. In natural waters, MLR and BLM criteria versions were strongly correlated. In contrast, the hardness-criteria version was often out of phase with the MLR and, depending on waterbody and season, could be either strongly overprotective or underprotective. The MLR-based USEPA-style chronic criterion appears to be more generally protective of ecosystems than other models. Environ Toxicol Chem 2023;00:1–35. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Pharmaceuticals and Personal Care Products in the Aquatic Environment: How Can Regions at Risk be Identified in the Future?

Abstract

Pharmaceuticals and personal care products (PPCPs) are an indispensable component of a healthy society. However, they are well established environmental contaminants, and many can elicit biological disruption in exposed organisms. It is now a decade since the Society of Environmental Toxicology and Chemistry (SETAC) published its landmark review of PPCPs in the environment (Boxall et al., 2012). Here we discuss key research priorities for the next 10 years with an aim on how regions where PPCPs pose the greatest risk to environmental and human health, either now or in the future, can be identified. Specifically, we discuss why this problem is of importance and review our current understanding of PPCPs in the aquatic environment. Foci include PPCP occurrence and what drives their environmental emission as well as our ability to both quantify and model their distribution. We highlight critical areas for future research including the involvement of citizen science for environmental monitoring and using modelling techniques to bridge the gap between research capacity and needs. As prioritisation of regions in need of environmental monitoring is needed to assess future/current risk, we also propose four criteria with which this may be achieved. Applying these criteria to available monitoring data we narrow the focus on where monitoring efforts for PPCPs are most urgent. Specifically, 19 cities across Africa, Central America, the Caribbean, and Asia were highlighted as priorities for future environmental monitoring and risk characterisation. Together, this informs our suggestion of four priority research questions for the next 10 years.

A toxicokinetic‐toxicodynamic modelling workflow assessing the quality of input mortality data

Abstract:

Toxicokinetic-toxicodynamic (TKTD) models simulate organismal uptake and elimination of a substance (TK) and its effects on the organism (TD). The Reduced General Unified Threshold model of Survival (GUTS-RED) is a TKTD modelling framework that is well established for aquatic risk assessment to simulate effects on survival. TKTD models are applied in three steps: parameterization based on experimental data (calibration), comparing predictions to independent data (validation) and prediction of endpoints under environmental scenarios. Despite a clear understanding of GUTS-RED predictions’ sensitivity to the model parameters, the influence of the input data on the quality of GUTS-RED calibration and validation is not systematically explored. We analyzed performance of GUTS-RED calibration and validation based on a unique, comprehensive dataset, covering different types of substances, exposure patterns and aquatic animal species taxa that are regularly used for risk assessment of plant protection products. We developed a software code to automatically calibrate and validate GUTS-RED against survival measurements from 59 toxicity tests and calculate selected model evaluation metrics. To assess whether specific survival data sets were better suited for calibration or validation, we applied a design where all possible combinations of studies for the same species-substance combination are used for calibration and validation. We found that uncertainty of calibrated parameters was lower when the full range of effects (i.e. from high survival to high mortality) was covered by input data. Increasing the number of toxicity studies used for calibration, further decreased parameter uncertainty. Including data from both acute and chronic studies as well as studies under pulsed and constant exposure in model calibrations improved model predictions on different types of validation data. Using our results we derive a workflow, including recommendations for the sequence of modelling steps from the selection of input data to a final judgement on the suitability of GUTS-RED for the dataset.

Interactive Effects of Copper‐Silver Mixtures at the Intestinal Epithelium of Rainbow Trout: an In‐Vitro Approach

ABSTRACT

While metals are present in mixture in the environment, metal toxicity studies are usually conducted on an individual metal basis. There is a paucity of data in the existing literature regarding specific metal-metal interactions and their effect on metal toxicity and bioavailability. Here, we studied interactions of silver-copper mixture at the intestinal epithelium using an intestinal cell line derived from rainbow trout (Oncorhynchus mykiss), the RTgutGC. Exposures were conducted in media containing different chloride concentrations (low chloride, 1 mM and high chloride, 146 mM) thus resulting in different metal speciation. Cytotoxicity was evaluated based on two endpoints, cell metabolic activity and cell membrane integrity. Silver-copper mixture toxicity was assessed using two designs: the independent action (IA) and concentration addition (CA). Metal mixture bioavailability was studied by exposing cells to 500 nM of Ag or Cu in single or mixture exposure (i.e., 500 nM of Cu plus 500 nM of Ag). We found an antagonistic effect in the low chloride medium and an additive/synergistic effect in the high chloride medium. We found that copper (Cu) dominates over silver (Ag) toxicity and bioavailability indicating a competitive inhibition when both metals are present as free metal ions in the exposure media which support our hypothesis. Our study also suggests different mechanisms of uptake of free metal ions and metal complexes. This study adds valuable information to our understanding of the role of metal speciation on metal mixture toxicity and bioavailability.

Bioaccumulation of Linear Siloxanes in Fish

Abstract

The bioaccumulation behavior, including the uptake, internal distribution, depuration, and biotransformation rates of three widely used linear methyl-siloxanes was investigated in Rainbow trout. Dietary uptake efficiencies of L3, L4, and L5 were 15% (3.3% SE), 8.6% (1.4% SE) and 15% (1.8% SE), respectively and for L3 and L4 were well below those of non-metabolizable reference chemicals with similar octanol-water partition coefficients, suggesting significant intestinal biotransformation of L3 and L4. Somatic biotransformation rate constants were 0.024 (0.003 SE) d-1 for L3; 0.0045 (0.0053 SE) d-1 for L4; and could not be determined for L5. Lipid-normalized biomagnification factors for L3, L4 and L5 were 0.24 (0.02 SE), 0.24 (0.01 SE) and 0.62 (0.05 SE) kg-lipid kg-lipid-1, respectively. Bioconcentration factors standardized to a 5% lipid content fish (BCF5%) for water in Canadian oligotrophic lakes with a dissolved organic carbon content of 7.1 mg L-1were 2787 (354 SE) for L3, 2689 (312 SE) for L4, and 1705 (418 SE) L kg-ww-1, respectively and 3085 (392 SE) for L3, 4227 (490 SE) for L4, and 3831 (938 SE) L kg-ww-1 in water with a dissolved organic carbon content of 2.0 mg L-1. A comparison of 238 bioaccumulation profiles for 166 different chemicals show that the bioaccumulation profiles for L3, L4 and L5 are vastly different from that of other very hydrophobic compounds found in the environment.

Towards Precision Ecotoxicology: Leveraging Evolutionary Conservation of Pharmaceutical and Personal Care Product Targets to Understand Adverse Outcomes Across Species and Life Stages

Abstract

Environmental science aims to protect biodiversity and ecosystem services, and our future ability to do that relies on a developing a precision ecotoxicology approach where we leverage the genetics and informatics of species to better understand and manage the risks of global pollution. A little over a decade ago, a workshop focusing on the risks of pharmaceuticals and personal care products (PPCPs) in the environment identified a priority research question, “What can be learned about the evolutionary conservation of PPCP targets across species and life stages in the context of potential adverse outcomes and effects?” Here we review the activities in this area over the past decade, consider prospects of more recent developments, and identify future research needs to develop next generation approaches for PPCPs and other global chemicals and waste challenges.

Photo‐Enhanced Oil Toxicity to Alcid Immune Function

Abstract

Oil spills are devastating to seabirds, causing high levels of mortality and toxic physiological effects, especially to immune function. Sunlight exposure can further enhance the toxicity of oil to marine species by generating photodegradation products. Photo-enhanced oil toxicity to marine birds has not been studied. Therefore, the goal of the present study was to investigate the toxicity and photo-enhanced toxicity of oil to lymphocyte proliferation, macrophage phagocytosis, and reactive oxygen species production in three alcid species, common murres (Uria aalge), tufted puffins (Fratercula cirrhata), and horned puffins (Fratercula corniculata). Intrinsic factors (species, age, and sex) had a more significant effect on lymphocyte proliferation than exposure to oil or photoactivated oil. Macrophage phagocytosis was significantly reduced in oil and photoactivated oil treatments, whereas hydrogen peroxide production was significantly increased. Interestingly, nonphotoactivated oil stimulated significantly more hydrogen peroxide than photoactivated oil. The results suggest that alcid immune function could be variably influenced during an oil spill depending on the species, sex, and age of the bird as well as the season and level of sunlight exposure. Environ Toxicol Chem 2023;00:1–11. © 2023 SETAC

Challenges and Recommendations in Assessing Potential Endocrine‐Disrupting Properties of Metals in Aquatic Organisms

Abstract

New tools and refined frameworks for identifying and regulating endocrine-disrupting chemicals (EDCs) are being developed as our scientific understanding of how they work advances. Although focus has largely been on organic chemicals, the potential for metals to act as EDCs in aquatic systems is receiving increasing attention. Metal interactions with the endocrine system are complicated because some metals are essential to physiological systems, including the endocrine system, and nonessential metals can have similar physiochemical attributes that allow substitution into or interference with these systems. Consequently, elevated metal exposure could potentially cause endocrine disruption (ED) but can also cause indirect effects on the endocrine system via multiple pathways or elicit physiologically appropriate compensatory endocrine-mediated responses (endocrine modulation). These latter two effects can be confused with, but are clearly not, ED. In the present study, we provide several case studies that exemplify the challenges encountered in evaluating the endocrine-disrupting (ED) potential of metals, followed by recommendations on how to meet them. Given that metals have multiple modes of action (MOAs), we recommend that assessments use metal-specific adverse outcome pathway networks to ensure that accurate causal links are made between MOAs and effects on the endocrine system. We recommend more focus on establishing molecular initiating events for chronic metal toxicity because these are poorly understood and would reduce uncertainty regarding the potential for metals to be EDCs. Finally, more generalized MOAs such as oxidative stress could be involved in metal interactions with the endocrine system, and we suggest it may be experimentally efficient to evaluate these MOAs when ED is inferred. These experiments, however, must provide explicit linkage to the ED endpoints of interest. Environ Toxicol Chem 2023;00:1–16. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Detection of Per‐ and Polyfluoroalkyl Substances in High‐Protein Food Products

Abstract

Per- and polyfluoroalkyl substances (PFAS) belong to the emerging class of persistent organohalogenated contaminants in the environment. We determined the levels of 10 PFAS in selected samples representing different food types, with a special focus on those rich in protein such as fish, meat and meat preparations, liver, eggs, and leguminous vegetables. Such determinations were based on the Quick Easy Cheap Effective Rugged Safe extraction procedure followed by micro-high-performance liquid chromatography–tandem mass spectrometry. The most frequently found was perfluorooctanoic acid, in 84% of the food samples. However, its maximum measured concentration was 0.50 ng g–1, in a herring sample. The highest concentrations were for perfluorobutanoic acid (35 ng g–1 measured in a pork liver sample) and perfluorooctane sulfonate (12 ng g–1 measured in a herring sample). Because these compounds may bioaccumulate in human tissues by dietary intake, further research into their impact on human health is called for. Environ Toxicol Chem 2023;00:1–10. © 2023 SETAC

Chronic Exposure to Environmentally Relevant Concentrations of Imidacloprid Impact Survival and Ecologically Relevant Behaviors of Fathead Minnow Larvae

Chronic Exposure to Environmentally Relevant Concentrations of Imidacloprid Impact Survival and Ecologically Relevant Behaviors of Fathead Minnow Larvae

“Potential for chronic exposure to imidacloprid to adversely affect fish larvae.”


Abstract

Imidacloprid (IM) has emerged as a contaminant of concern in several areas within the United States due to its frequent detection in aquatic ecosystems and its pseudo-persistence, which pose potential risks to nontarget species. We evaluated the sublethal toxicity of IM to fathead minnow larvae following chronic exposure beginning just after fertilization. Our in silico analysis and in vivo bioassays suggest that IM has a low binding affinity for the vertebrate nicotinate acetylcholine receptor (nAChR), as expected. However, chronic exposure to ≥0.16 µg IM/L reduced survival by 10%, and exposure to ≥18 µg IM/L reduced survival by approximately 20%–40%. Surviving fish exposed to ≥0.16 µg IM/L showed reduced growth, altered embryonic motor activity, and premature hatching. Furthermore, a significant proportion of fish exposed to ≥0.16 µg IM/L were slower to respond to vibrational stimuli and slower to swim away, indicating that chronic exposure to IM has the potential to impair the ability of larvae to escape predation. The adverse health effects we observed indicate that chronic exposure to environmentally relevant concentrations of IM may elicit sublethal responses that culminate in a significant increase in mortality during early life stages, ultimately translating to reduced recruitment in wild fish populations. Environ Toxicol Chem 2023;42:2184–2192. © 2023 SETAC