Abstract

Pharmaceuticals and personal care products (PPCPs) occur as variable mixtures in surface waters receiving discharges of human and animal wastes. A key question identified a decade ago is how to assess the effects of long-term exposures of these PPCP mixtures on nontarget organisms. We review the recent progress made on assessing the aquatic ecotoxicity of PPCP mixtures—with a focus on active pharmaceutical ingredients—and the challenges and research needs that remain. New knowledge has arisen from the use of whole-mixture testing combined with component-based approaches, and these studies show that mixtures often result in responses that meet the concentration addition model. However, such studies have mainly been done on individual species over shorter time periods, and longer-term, multispecies assessments remain limited. The recent use of targeted and nontargeted gene analyses has improved our understanding of the diverse pathways that are impacted, and there are promising new “read-across” methods that use mammalian data to predict toxicity in wildlife. Risk assessments remain challenging given the paucity of ecotoxicological and exposure data on PPCP mixtures. As such, the assessment of PPCP mixtures in aquatic environments should remain a priority given the potential for additive—as well as nontarget—effects in nontarget organisms. In addition, we need to improve our understanding of which species, life stages, and relevant endpoints are most sensitive to which types of PPCP mixtures and to expand our knowledge of environmental PPCP levels in regions of the globe that have been poorly studied to date. We recommend an increased use of new approach methodologies, in particular “omics,” to advance our understanding of the molecular mechanics of mixture effects. Finally, we call for systematic research on the role of PPCP mixtures in the development of antimicrobial resistance. Environ Toxicol Chem 2023;00:1–10. © 2023 SETAC.

Abstract

Bioavailability models, for example, multiple linear regressions (MLRs) of water quality parameters, are increasingly being used to develop bioavailability-based water quality criteria for metals. However, models developed for the Northern Hemisphere cannot be adopted for Australia and New Zealand without first validating them against local species and local water chemistry characteristics. We investigated the applicability of zinc chronic bioavailability models to predict toxicity in a range of uncontaminated natural waters in Australia and New Zealand. Water chemistry data were compiled to guide a selection of waters with different zinc toxicity-modifying factors. Predicted toxicities using several bioavailability models were compared with observed chronic toxicities for the green alga Raphidocelis subcapitata and the native cladocerans Ceriodaphnia cf. dubia and Daphnia thomsoni. The most sensitive species to zinc in five New Zealand freshwaters was R. subcapitata (72-h growth rate), with toxicity ameliorated by high dissolved organic carbon (DOC) or low pH, and hardness having a minimal influence. Zinc toxicity to D. thomsoni (reproduction) was ameliorated by both high DOC and hardness in these same waters. No single trophic level–specific effect concentration, 10% (EC10) MLR was the best predictor of chronic toxicity to the cladocerans, and MLRs based on EC10 values both over- and under-predicted zinc toxicity. The EC50 MLRs better predicted toxicities to both the Australian and New Zealand cladocerans to within a factor of 2 of the observed toxicities in most waters. These findings suggest that existing MLRs may be useful for normalizing local ecotoxicity data to derive water quality criteria for Australia and New Zealand. The final choice of models will depend on their predictive ability, level of protection, and ease of use. Environ Toxicol Chem 2023;00:1–16. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Lethal and sublethal effects of pesticides on nontarget organisms are one of the causes of the current decline of many insect species. However, research in the past decades has focused primarily on pollinators, although other beneficial nontarget organisms such as parasitic wasps may also be affected. We studied the sublethal effects of the four insecticides acetamiprid, dimethoate, flupyradifurone, and sulfoxaflor on pheromone-mediated sexual communication and olfactory host finding of the parasitic wasp Nasonia vitripennis. All agents target cholinergic neurons, which are involved in the processing of chemical information by insects. We applied insecticide doses topically and tested the response of treated wasps to sex pheromones and host-associated chemical cues. In addition, we investigated the mating rate of insecticide-treated wasps. The pheromone response of females surviving insecticide treatment was disrupted by acetamiprid (≥0.63 ng), dimethoate (≥0.105 ng), and flupyradifurone (≥21 ng), whereas sulfoxaflor had no significant effects at the tested doses. Olfactory host finding was affected by all insecticides (acetamiprid ≥1.05 ng, dimethoate ≥0.105 ng, flupyradifurone ≥5.25 ng, sulfoxaflor ≥0.52 ng). Remarkably, females treated with ≥0.21 ng dimethoate even avoided host odor. The mating rate of treated N. vitripennis couples was decreased by acetamiprid (6.3 ng), flupyradifurone (≥2.63 ng), and sulfoxaflor (2.63 ng), whereas dimethoate showed only minor effects. Finally, we determined the amount of artificial nectar consumed by N. vitripennis females within 48 h. Considering this amount (∼2 µL) and the maximum concentrations of the insecticides reported in nectar, tested doses can be considered field-realistic. Our results suggest that exposure of parasitic wasps to field-realistic doses of insecticides targeting the cholinergic system reduces their effectiveness as natural enemies by impairing the olfactory sense. Environ Toxicol Chem 2023;00:1–12. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Perfluoroalkyl carboxylic and sulfonic acids (PFCAs and PFSAs, respectively) have low acid dissociation constant values and are, therefore, deprotonated under most experimental and environmental conditions. Hence, the anionic species dominate their partitioning between water and organic phases, including octanol and phospholipid bilayers which are often used as model systems for environmental and biological matrices. However, data for solvent–water (SW) and membrane–water partition coefficients of the anion species are only available for a few per- and polyfluoroalkyl substances (PFAS). In the present study, an equation is derived using a Born-Haber cycle that relates the partition coefficients of the anions to those of the corresponding neutral species. It is shown via a thermodynamic analysis that for carboxylic acids (CAs), PFCAs, and PFSAs, the log of the solvent–water partition coefficient of the anion, log K _SW(A⁻), is linearly related to the log of the solvent–water partition coefficient of the neutral acid, log K _SW(HA), with a unity slope and a solvent-dependent but solute-independent intercept within a PFAS (or CA) family. This finding provides a method for estimating the partition coefficients of PFCAs and PFSAs anions using the partition coefficients of the neutral species, which can be reliably predicted using quantum chemical methods. In addition, we have found that the neutral octanol–water partition coefficient, log K _OW, is linearly correlated to the neutral membrane–water partition coefficient, log K _MW; therefore, log K _OW, being a much easier property to estimate and/or measure, can be used to predict the neutral log K _MW. Application of this approach to K _OW and K _MW for PFCAs and PFSAs demonstrates the utility of this methodology for evaluating reported experimental data and extending anion property data for chain lengths that are unavailable. Environ Toxicol Chem 2023;00:1–12. © 2023 SETAC

Abstract

The potential of pharmaceuticals and personal care products to alter the behavior of aquatic organisms is a growing concern. To assess the actual effect of these substances on aquatic organisms, a simple but effective behavioral test is required. We devised a simple behavioral (Peek-A-Boo) test to assess the effect of anxiolytics on the behavior of a model fish (medaka, Oryzias latipes). In the Peek-A-Boo test, we investigated the response of medaka to an image of a predator fish (donko fish, Odontobutis obscura). The test revealed that the time taken for test medaka exposed to diazepam (0.8, 4, 20, or 100 µg/L) to approach the image was shorter by a factor of 0.22 to 0.65, and the time spent in the area close to the image was longer by a factor of 1.8 to 2.7 than in the solvent control group for all diazepam exposure groups (p < 0.05). Hence, we confirmed that the test could detect changes in medaka behavior caused by diazepam with high sensitivity. The Peek-A-Boo test we devised is a simple behavioral test with high sensitivity for fish behavioral alteration. Environ Toxicol Chem 2023;00:1–6. © 2023 SETAC.

Temperature alters the toxicity of polycyclic aromatic compounds to Stage I American lobster larvae, and these temperature-based differences in toxicity are important data inputs for oil spill effects models.

Abstract

Polycyclic aromatic compounds (PACs) present in the water column are considered to be one of the primary contaminant groups contributing to the toxicity of a crude oil spill. Because crude oil is a complex mixture composed of thousands of different compounds, oil spill models rely on quantitative structure–activity relationships like the target lipid model to predict the effects of crude oil exposure on aquatic life. These models rely on input provided by single species toxicity studies, which remain insufficient. Although the toxicity of select PACs has been well studied, there is little data available for many, including transformation products such as oxidized hydrocarbons. In addition, the effect of environmental influencing factors such as temperature on PAC toxicity is a wide data gap. In response to these needs, in the present study, Stage I lobster larvae were exposed to six different understudied PACs (naphthalene, fluorenone, methylnaphthalene, phenanthrene, dibenzothiophene, and fluoranthene) at three different relevant temperatures (10, 15, and 20 °C) all within the biological norms for the species during summer when larval releases occur. Lobster larvae were assessed for immobilization as a sublethal effect and mortality following 3, 6, 12, 24, and 48 h of exposure. Higher temperatures increased the rate at which immobilization and mortality were observed for each of the compounds tested and also altered the predicted critical target lipid body burden, incipient median lethal concentration, and elimination rate. Our results demonstrate that temperature has an important influence on PAC toxicity for this species and provides critical data for oil spill modeling. More studies are needed so oil spill models can be appropriately calibrated and to improve their predictive ability. Environ Toxicol Chem 2023;00:1–11. © 2023 SETAC

Abstract

Marine turtles face numerous anthropogenic threats, including that of chemical contaminant exposure. The ecotoxicological impact of toxic metals is a global issue facing Chelonia mydas in coastal sites. Local investigation of C. mydas short-term blood metal profiles is an emerging field, while little research has been conducted on scute metal loads as potential indicators of long-term exposure. The aim of the present study was to investigate and describe C. mydas blood and scute metal profiles in coastal and offshore populations of the Great Barrier Reef. This was achieved by analyzing blood and scute material sampled from local C. mydas populations in five field sites, for a suite of ecologically relevant metals. By applying principal component analysis and comparing coastal sample data with those of reference intervals derived from the control site, insight was gleaned on local metal profiles of each population. Blood metal concentrations in turtles from coastal sites were typically elevated when compared with levels recorded in the offshore control population (Howick Island Group). Scute metal profiles were similar in Cockle Bay, Upstart Bay, and Edgecumbe Bay, all of which were distinct from that of Toolakea. Some elements were reported at similar concentrations in blood and scutes, but most were higher in scute samples, indicative of temporal accumulation. Coastal C. mydas populations may be at risk of toxic effects from metals such as Co, which was consistently found to be at concentrations magnitudes above region-specific reference intervals. Environ Toxicol Chem 2023;00:1–14. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

Per- and polyfluoroalkyl substances (PFAS) and mercury (Hg) are harmful compounds that are widely present in the environment, partly due to spills and atmospheric pollution. The presence of PFAS and Hg in the tissues of animals that are harvested by rural and Indigenous Alaskans is of great concern, yet fish in Arctic Alaska have not previously been assessed for concentrations of PFAS. Fish species of subsistence and recreational importance were collected from nearshore Beaufort and Chukchi Sea, Alaska habitats and assessed for PFAS and total mercury concentrations [THg]. We found multiple PFAS compounds present at low levels (<3 μg/kg) in the muscle tissue of inconnu, broad whitefish, Dolly Varden char, Arctic flounder, saffron cod, humpback whitefish, and least cisco. In addition, [THg] levels in these fish were well below levels triggering local fish consumption guidelines (<170 μg/kg). These initial results indicate no evidence of the Alaska Arctic nearshore fish species examined as an avenue of PFAS or Hg exposure to people who harvest them. However, sources and trends of these contaminants in the Arctic require further investigation. Environ Toxicol Chem 2023;00:1–7. © 2023 SETAC

CD-1 mice were exposed to six per- and polyfluoroalkyl substance (PFAS)–free aqueous film-forming foam (AFFF) products and one PFAS-containing AFFF product. Relative liver weight in male mice presented a graded response across products and indicates that PFAS-free AFFF products have a different mechanism of toxicity from PFAS-containing AFFF products and that PFAS-free AFFF products show limited effects overall.

Abstract

The comparative toxicity of six per- and polyfluoroalkyl substance (PFAS)–free and one PFAS-containing aqueous film-forming foam (AFFF) was evaluated in an outbred mouse species as well as several in vitro assays. The in vivo toxicological profile of PFAS-free AFFFs in short-term, high-concentration exposures is different than that of a PFAS-containing AFFF. The PFAS-containing reference product induced increased liver weights, while the PFAS-free AFFFs were linked to either decreased or unaffected relative liver weights. The in vitro toxicological profile across PFAS-free AFFFs was uniform except in the Microtox® assay, where thresholds were variable and spanned several orders of magnitude. This direct comparison of products through short-term toxicity tests and in vitro screenings represents early data to support evaluation of potential regrettable substitutions when selecting alternative PFAS-free AFFFs. Further work in diverse taxa (e.g., aquatic organisms, terrestrial invertebrates, birds) and mammalian studies capturing sensitive life stages will refine and expand this data set across a range of risk-relevant toxicological endpoints. Environ Toxicol Chem 2023;00:1–11. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Enhancing chemical safety assessment with high-precision ecotoxicology predictions.

Abstract

The extrapolation of biological data across species is a key aspect of biomedical research and drug development. In this context, comparative biology considerations are applied with the goal of understanding human disease and guiding the development of effective and safe medicines. However, the widespread occurrence of pharmaceuticals in the environment and the need to assess the risk posed to wildlife have prompted a renewed interest in the extrapolation of pharmacological and toxicological data across the entire tree of life. To address this challenge, a biological “read-across” approach, based on the use of mammalian data to inform toxicity predictions in wildlife species, has been proposed as an effective way to streamline the environmental safety assessment of pharmaceuticals. Yet, how effective has this approach been, and are we any closer to being able to accurately predict environmental risk based on known human risk? We discuss the main theoretical and experimental advancements achieved in the last 10 years of research in this field. We propose that a better understanding of the functional conservation of drug targets across species and of the quantitative relationship between target modulation and adverse effects should be considered as future research priorities. This pharmacodynamic focus should be complemented with the application of higher-throughput experimental and computational approaches to accelerate the prediction of internal exposure dynamics. The translation of comparative (eco)toxicology research into real-world applications, however, relies on the (limited) availability of experts with the skill set needed to navigate the complexity of the problem; hence, we also call for synergistic multistakeholder efforts to support and strengthen comparative toxicology research and education at a global level. Environ Toxicol Chem 2023;00:1–13. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.