The Use of Mechanistic Population Models in Metal Risk Assessment: Combined Effects of Copper and Food Source on Lymnaea stagnalis Populations.

Environmental risk assessment (ERA) of chemicals aims to protect populations, communities, and ecosystems. Population models are considered more frequent in ERA because they can bridge the gap between the individual and the population level. Lymnaea stagnalis (the great pond snail) is an organism that is particularly sensitive to various metals, including copper (Cu). In addition, the sensitivity of this species to Cu differs between food sources. The first goal of the present study was to investigate whether we could explain the variability in sensitivity between food sources (lettuce and fish flakes) at the individual level with a dynamic energy budget (DEB) model. By adapting an existing DEB model and calibrating it with Cu toxicity data, thereby combining information from 3 studies and 2 endpoints (growth and reproduction), we put forward inhibition of energy assimilation as the most plausible physiological mode of action (PMoA) of Cu. Furthermore, the variation in Cu sensitivity between both food sources was considerably lower at the PMoA level than at the individual level. Higher Cu sensitivity at individual level under conditions of lower food quality or availability appears to emerge from first DEB principles when inhibition of assimilation is the PMoA. This supports the idea that DEB explained Cu sensitivity variation between food sources. Our second goal was to investigate whether this food source effect propagated to the population level. By incorporating DEB in an individual-based model (IBM), population-level effects were predicted. Based on our simulations, the food source effect was still present at the population level, albeit less prominently. Finally, we compared predicted population-level effect concentration, x% (ECx) values with individual-level ECx values for different studies. Using the DEB-IBM, the range of effect concentrations decreased significantly: at the individual level, the difference in chronic EC10 values between studies was a factor of 70 (1.13-78 µg dissolved Cu/L), whereas at the population level the difference was a factor of 15 (2.9-44.6 µg dissolved Cu/L). To improve interstudy comparability, a bioavailability correction for differences in water chemistry was performed with a biotic ligand model. This further decreased the variation, down to a factor of 7.4. Applying the population model in combination with a bioavailability correction thus significantly decreased the variability of chronic effect concentrations of Cu for L. stagnalis. Overall, the results of the present study illustrate the potential usefulness of transitioning to a more modeling-based environmental risk assessment. Environ Toxicol Chem 2019;00:1-16. © 2019 SETAC.

Vlaeminck K ，Viaene KPJ ，Van Sprang P ，Baken S ，De Schamphelaere KAC ... -  《-》

Using a dynamic energy budget model to investigate the physiological mode of action of lead (Pb) to Lymnaea stagnalis.

Lymnaea stagnalis is a notably sensitive species for a variety of metals, including lead (Pb). However, the mechanism(s) of lead toxicity to L. stagnalis currently remain incompletely understood. Under dynamic energy budget (DEB) theory, different physiological modes of action (PMoAs) result in the emergence of distinct changes to the life histories of exposed organisms. This work aims to better understand the PMoA of lead toxicity to L. stagnalis by applying DEB modeling to previously published datasets. After calibration, the model was utilized to evaluate the relative likelihood of several PMoAs. Assuming decreased assimilation, the L. stagnalis DEB model was able to capture most, but not all, trends in experimentally observed endpoints, including growth, reproduction, and food ingestion. The weight-of-evidence suggests that decreased assimilation via a decrease in food ingestion is the most plausible PMoA for chronic lead toxicity in L. stagnalis. Collectively, our results illustrate how mechanistic modeling can create added value for conventional individual-level toxicity test data by enabling inferences about potential physiological mechanisms of toxicity.

Weighman K ，Viaene K ，Koch J ，De Schamphelaere K ... -  《-》

The toxicity and physiological effects of copper on the freshwater pulmonate snail, Lymnaea stagnalis.

Several recent studies have demonstrated that the freshwater pulmonate snail Lymnaea stagnalis is extremely sensitive to metals (Co, Ni, Pb) in chronic exposures. The objective of the current study was to evaluate the acute and chronic sensitivity of L. stagnalis to Cu and investigate the underlying mechanism(s) of toxic action. A 96-h LC50 of 31μg L(-1) Cu was estimated indicating L. stagnalis was moderately acutely sensitive to Cu relative to other aquatic organisms. However, in a 30-day chronic exposure using juvenile snails an EC20 of 1.8μg L(-1) Cu was estimated for snail growth making L. stagnalis the most sensitive organism tested to date for Cu. Hardness-based and BLM-based water quality criteria for Cu at the water quality conditions used in this study were 7.8 and 1.5μg L(-1), respectively, indicating L. stagnalis is significantly under-protected by hardness-based WQC. Investigations into the mechanism(s) of toxic action for Cu were conducted on young adult snails necessitating higher Cu exposures. Exposure to Cu at 12μg L(-1) resulted in no detectable effects on hemolymph osmolality, net Ca(2+) uptake, titratable acid excretion, or ammonia excretion. Exposure to 48μg L(-1) Cu was shown to significantly reduce (91%) net Ca(2+) uptake which is strongly correlated with shell deposition and corresponding snail growth. Snails exposed to 48μg L(-1) Cu also exhibited reduced ammonia excretion, a marked hemolymph acidosis, and a compensatory increase in titratable acid excretion. The reduction in net Ca(2+) uptake was hypothesized to be a secondary effect of Cu-induced inhibition of carbonic anhydrase, but no reduction in carbonic anhydrase activity was detected. Overall, it remains unclear whether inhibition of Ca(2+) uptake is a direct result of Cu exposure or, along with the other observed physiological effects, is secondary to an unidentified primary mode of toxic action. Given the hypersensitivity of L. stagnalis to Cu, further study into the mechanisms of action and effects of varying water chemistry on Cu toxicity is clearly warranted.

Brix KV ，Esbaugh AJ ，Grosell M 《COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY》

Extrapolating Metal (Cu, Ni, Zn) Toxicity from Individuals to Populations Across Daphnia Species Using Mechanistic Models: The Roles of Uncertainty Propagation and Combined Physiological Modes of Action.

Mechanistic effect modeling is a promising tool to improve the ecological realism of environmental risk assessment. An open question for the mechanistic modeling of metal toxicity is whether the same physiological mode of action (PMoA) could be assumed for closely related species. The implications of various modeling choices, such as the use of parameter point estimates and assumption of simplistic toxicodynamic models, are largely unexplored. We conducted life-table experiments with Daphnia longispina, Daphnia magna, and Daphnia pulex exposed to the single metals Cu, Ni, and Zn, and calibrated toxicokinetic-toxicodynamic (TKTD) models based on dynamic energy budget theory. We developed TKTD models with single and combined PMoAs to compare their goodness-of-fit and predicted population-level sensitivity. We identified the PMoA reproduction efficiency as most probable in all species for Ni and Zn, but not for Cu, and found that combined-PMoA models predicted higher population-level sensitivity than single-PMoA models, which was related to the predicted individual-level sensitivity, rather than to mechanistic differences between models. Using point estimates of parameters, instead of sampling from the probability distributions of parameters, could also lead to differences in the predicted population-level sensitivity. According to model predictions, apical chronic endpoints (cumulative reproduction, survival) are conservative for single-metal population effects across metals and species. We conclude that the assumption of an identical PMoA for different species of Daphnia could be justified for Ni and Zn, but not for Cu. Single-PMoA models are more appropriate than combined-PMoA models from a model selection perspective, but propagation of the associated uncertainty should be considered. More accurate predictions of effects at low concentrations may nevertheless motivate the use of combined-PMoA models. Environ Toxicol Chem 2024;43:338-358. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Hansul S ，Fettweis A ，Smolders E ，Schamphelaere K ... -  《-》

The Unexpected Absence of Nickel Effects on a Daphnia Population at 3 Temperatures is Correctly Predicted by a Dynamic Energy Budget Individual-Based Model.

Recent studies have shown that temperature affects chronic nickel (Ni) toxicity to Daphnia magna at the individual (apical) level. However, the effect of temperature on Ni toxicity to D. magna at the population level is unknown. The present study investigated whether the effect of temperature on chronic Ni toxicity to D. magna assessed on apical endpoints can be extrapolated to the population level. The results of the population experiment showed no consistent Ni effects on total D. magna population abundance at 15, 20, and 25 °C, although the Ni concentrations tested were previously reported to significantly reduce reproduction in D. magna individuals. This result supports the idea that ecological risk assessment should not extrapolate as such from apical endpoints to the population level. A dynamic energy budget individual-based model (DEB-IBM) was calibrated using apical Ni toxicity data at 15, 20, and 25 °C. The goal was to investigate whether the calibrated DEB-IBM would be able to predict the unexpected absence of effects at the population level and to further investigate the effect of temperature on Ni toxicity to a D. magna population. At the population level, the calibrated DEB-IBM correctly predicted the unexpected absence of an effect of Ni on a D. magna population. Detailed analysis of simulation output suggests that the predicted lower Ni sensitivity at the population level occurs because Ni-induced mortality is compensated by reduced starvation (less intraspecific competition). Extrapolated median effective concentration (EC50) values for population density predicted that the effect of temperature on Ni toxicity to D. magna populations was smaller (1.9-fold higher at 25 °C than at 15 °C) than on Ni toxicity to D. magna apical reproduction (the EC50 is 6.5-fold higher at 25 °C than at 15 °C). These results show that the DEB-IBM can help to replace population experiments by in silico simulations and to optimize the experimental design of population studies. Environ Toxicol Chem 2019;38:1423-1433. © 2019 SETAC.

Pereira CMS ，Vlaeminck K ，Viaene K ，De Schamphelaere KAC ... -  《-》