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.