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.

Metal Mixture Toxicity of Ni, Cu, and Zn in Freshwater Algal Communities and the Correlation of Single-Species Sensitivities Among Single Metals: A Comparative Analysis.

The effects assessment of metals is mainly based on data of single metals on single species, thereby not accounting for effects of metal mixtures or effects of species interactions. Both of these effects were tested in combination, thereby hypothesizing that the sensitivity of a community to synergistic mixture toxicity depends on the correlation of single-species sensitivities among the single metals. Single-metal and metal-mixture effects were tested in full concentration-response experiments (fixed ray of 1:1:3 and 5:1:13 mass ratio Ni:Cu:Zn) on eight single freshwater algal species and 14 algal communities of four species each. The mean correlation of single-species median effect concentrations among the single metals (Ni-Cu, Cu-Zn, and Zn-Ni) for all species in a community ( r ̅ ) ranged from -0.4 to 0.9 among the communities; most of these (12/14) were positive. Functional endpoints (total biomass) were overall less sensitive than structural endpoints (Bray-Curtis similarity index) for communities with positively correlated single-species sensitivities among the single metals ( r ̅ > 0.33 ), suggesting that such correlations indicate functional redundancy under metal-mixture stress. Antagonistic metal-mixture interactions were predominantly found in single species, whereas metal-mixture interactions were antagonistic and surprisingly synergistic for the communities, irrespective of the reference mixture model used (concentration addition or independent action). The mixture interactions close to the carrying capacity (day 7) of communities gradually shifted from antagonism to more noninteractions with increasing correlation of single-species sensitivities among the single metals. Overall, this suggests that functional redundancy under mixed-metal stress comes at the cost of reduced biodiversity and that synergisms can emerge at the community level without any synergisms on the single-species level. Environ Toxicol Chem 2023;42:2666-2683. © 2023 SETAC.

Interactive Metal Mixture Toxicity to Daphnia magna Populations as an Emergent Property in a Dynamic Energy Budget Individual-Based Model.

Environmental risk assessment of metal mixtures is challenging due to the large number of possible mixtures and interactions. Mixture toxicity data cannot realistically be generated for all relevant scenarios. Therefore, methods for prediction of mixture toxicity from single-metal toxicity data are needed. We tested how well toxicity of Cu-Ni-Zn mixtures to Daphnia magna populations can be predicted based on the Dynamic Energy Budget theory with an individual-based model (DEB-IBM), assuming non-interactivity of metals on the physiological level. We exposed D. magna populations to Cu, Ni, and Zn and their mixture at a fixed concentration ratio. We calibrated the DEB-IBM with single-metal data and generated blind predictions of mixture toxicity (population size over time), with account for uncertainty. We compared the predictive performance of the DEB-IBM with respect to mixture effects on population density and population growth rates with that of two reference models applied on the population level, independent action and concentration addition. Our inferred physiological modes of action (pMoA) differed from literature-reported pMoAs, raising the question of whether this is a result of different model selection approaches, intraspecific variability, or whether different pMoAs might actually drive toxicity in a population context. Observed mixture effects were concentration- and endpoint-dependent. The independent action was overall more accurate than the concentration addition but concentration addition-predicted effects on population growth rate were slightly better. The DEB-IBM most accurately predicted effects on 6-week density, including antagonistic effects at high concentrations, which emerged from non-interactivity at the physiological level. Mixture effects on initial population growth rate appear to be more difficult to predict. To explain why model accuracy is endpoint-dependent, relationships between individual-level and population-level endpoints should be illuminated. Environ Toxicol Chem 2021;40:3034-3048. © 2021 SETAC.

Correlated Ni, Cu, and Zn Sensitivities of 8 Freshwater Algal Species and Consequences for Low-Level Metal Mixture Effects.

Predicting metal sensitivities and metal mixture interactions for species within each trophic level is essential to understand the effects of metals at the ecosystem level. The present study was set up to explore the correlations of metal sensitivities among species and if these sensitivities or metal mixture interactions are related to growth or morphological traits. The toxicity of Ni, Cu, and Zn on algal growth was tested for 8 freshwater algal species when dosed singly and in combinations in phosphorus-limiting static systems. The metal sensitivities on specific growth rate (10% effect concentrations expressed as free ion activities) varied 2 to 3 orders of magnitude among species depending on metal. These sensitivities were unrelated (p > 0.05) to their specific growth rate (0.7-1.8 d-1 ) or cell volume (100 -103 m3 cell-1 ). Species-specific differences in one or more toxicokinetic and/or toxicodynamic (TKTD) processes are likely at the basis of this variation. The log-transformed metal sensitivities positively correlated (p < 0.1) among the species in all 3 binary combinations (Ni-Cu, Ni-Zn, and Cu-Zn), suggesting that species have correlated TKTD rates for these metals. Furthermore, they would also predict stronger effects of metal mixtures on algal community biodiversity than what would be expected without a positive correlation. Low-level metal mixture effects varied similarly, largely among species and mixture interactions that were highly variable: ranging from synergistic to antagonistic relative to independent action during exponential growth, whereas mixture interactions at 10% effect shifted toward additivity/synergism relative to concentration addition at carrying capacity. Some evidence was found for stronger synergistic mixture effects in smaller species. Overall, the present study highlights the importance of incorporating more species in sensitivity distributions and accounting for mixture toxicity in risk assessment. Environ Toxicol Chem 2021;40:2015-2025. © 2021 SETAC.

Zinc toxicity to Daphnia magna in a two-species microcosm can be predicted from single-species test data: The effects of phosphorus supply and pH.

Ecological interactions and abiotic stress factors may significantly affect species sensitivities to toxicants, and these are not incorporated in standard single-species tests. The present study tests whether a model, calibrated solely on single-species data, can explain abiotic stress factors in a two-species microcosm, a test applied to the effects of nutritional stress (phosphorus [P] limitation) on zinc (Zn) toxicity to Daphnia magna. A population model was developed based on P- and Zn-dependent algal and daphnid growth. Two separate two-species (phytoplankton Pseudokirchneriella subcapitata and consumer D. magna) microcosm experiments with P × Zn factorial combinations and a different pH (7.3 and 7.8) were set up to validate the model. The 21-d daphnid population size was considerably reduced by increased Zn and by decreased P supply, with a significant (p < 0.001) interaction between the 2 factors. The observed median effective concentration (EC50) of Zn on D. magna population size varied 12-fold (25 to 310 µg Zn L-1 ), with the lowest EC50 values found at the highest pH and high P treatments. For both experiments, Zn toxicity to D. magna was correctly predicted within a factor of 2 for EC50 values, and this is explained by the model through 1) a higher phytoplankton Zn sensitivity at higher pH, affecting food supply to D. magna, and 2) an increased algal P content at higher Zn, offering a nutritional benefit to daphnids that counteracts direct Zn toxicity under P limitation. The present study illustrates that indirect effects of Zn via producer-consumer relationships can outweigh the direct toxic effects and that models calibrated solely on single-species test data can help with interpreting these results in two-species systems. Environ Toxicol Chem 2018;37:2153-2164. © 2018 SETAC.