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Marine mammals, due to their long life span, key position in the food web, and large lipid deposits, often face significant health risks from accumulating contaminants. This systematic review examines published literature on pollutant-induced adverse health effects in the International Union for Conservation of Nature (IUCN) red-listed marine mammal species. Thereby, identifying gaps in literature across different extinction risk categories, spatial distribution and climatic zones of studied habitats, commonly used methodologies, researched pollutants, and mechanisms from cellular to population levels. Our findings reveal a lower availability of exposure-effect data for higher extinction risk species (critically endangered 16%, endangered 15%, vulnerable 66%), highlighting the need for more research. For many threatened species in the Southern Hemisphere pollutant-effect relationships are not established. Non-destructively sampled tissues, like blood or skin, are commonly measured for exposure assessment. The most studied pollutants are POPs (31%), metals (30%), and pesticides (17%). Research on mixture toxicity is scarce while pollution-effect studies primarily focus on molecular and cellular levels. Bridging the gap between molecular data and higher-level effects is crucial, with computational approaches offering a high potential through in vitro to in vivo extrapolation using (toxico-)kinetic modelling. This could aid in population-level risk assessment for threatened marine mammals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Cell-based toxicity testing has emerged as a useful tool in (eco)toxicological research, allowing the ethical assessment of the effects of contaminants such as trace metals on marine megafauna. However, metal interactions with various dissolved ligands in the microplate environment may influence the effective exposure concentrations. Hence, the cells are not exposed to the nominal concentrations within the test system. This study aimed to establish and evaluate the effectiveness of cell-based bioassays for investigating the toxicity of selected metals in dugongs through the following objectives: (1) measure the cytotoxic potential of cadmium (Cd 2+ ), and chromium (Cr 6+ ) to dugong skin cell cultures, (2) investigate the interactions between media constituents and selected trace metals in cell-based bioassays, and (3) evaluate the risk to a free-ranging population of dugong based on effect values. Chromium was the most toxic of the metals tested (EC 50  = 1.14 µM), followed by Cd (EC 50  = 6.35 µM). Assessment of ultrafiltered (< 3 kDa) exposure media showed that 1% and 92.5% of Cr and Cd were associated with larger organic components of the media. Further, the binding of Cd to media constituents was calculated to underestimate Cd toxicity in cell-based assays by an order of magnitude. This understanding of metal partitioning in cell-based bioassays provides a more accurate method for assessing toxicity in cell-based bioassays. In addition, this study illustrated that dugong cells are more sensitive to Cr and Cd than other marine wildlife species. The chemical risk assessment found the dugong population in Moreton Bay to be at high risk from Cd exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Although the recovery and beneficial reuse of organic matter and nutrients from sludge represents an important move towards environmental sustainability, the accumulation of chemicals in biosolid-amended soils could pose serious environmental and human health risks. However, (eco)toxicological profiling of complex chemical mixtures in biosolids is currently limited. In particular, the effect of anaerobic digestion (AD), the most common stabilization process for sewage sludge, on the (eco)toxicity of those complex mixtures is poorly studied. In this work, we fill this research gap by applying an effect-based monitoring approach to screen sludge samples (n = 4) from a full-scale sewage treatment plant before and after conventional mesophilic (37 °C) AD using a battery of cell-based in vitro bioassays for four types of hormonal activity: estrogenic, androgenic, progestagenic and glucocorticoid activity, both in agonist and antagonist modes. We detected estrogenic, glucocorticoid and anti-progestagenic activity in all sludge samples. The glucocorticoid and anti-progestagenic activity remained mostly unchanged after AD treatment, but estrogenicity increased three-fold, likely as a result of bioactivation processes in the digestor. This study presents the first report on the concentration and fate of glucocorticoid and anti-progestagenic activity in AD. Future research should apply bioanalytical tools to a wider range of sludge samples to get a better understanding of the typical hormonal activity in sludge and develop effect-based trigger (EBT) values for biosolids to help interpret the risk posed by the hormonal activity detected in sludge., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Environmental contaminants pose serious health threats to marine megafauna species, yet methods defining exposure threshold limits are lacking. Here, a three-pillar chemical risk assessment framework is presented based on (1) species- and chemical-specific lifetime bioaccumulation modelling, (2) non-destructive in vitro and in vivo toxicity threshold assessment, and (3) chemical risk quantification. We used the effects of cadmium (Cd) in green sea turtles (Chelonia mydas) as a proof of concept to evaluate the quantitative mechanistic modelling approach. A physiologically-based kinetic (PBK) model simulated Cd tissue concentrations (liver, kidney, muscle, fat, brain, scute, and 'rest of the body') in C.mydas. The validated PBK model then translated species-specific in vitro results to in vivo effects. The results showed that the resilience of C.mydas towards Cd kidney toxicity is age-dependent and differs with changing physiology and feeding ecology. Using the model in reverse mode, a steady-state exposure threshold of 0.1 µg/g dry weight Cd in forage was derived and compared to real-world exposure scenarios. Three out of the four globally distinct C.mydas populations assessed are exposed to Cd levels above this threshold limit. This approach can be adapted to other marine species and chemicals to prioritize measures for managing potentially harmful chemical exposures., (Copyright © 2021 Elsevier B.V. All rights reserved.)