Interaction between nickel and cobalt toxicity in Enchytraeus crypticus is due to competitive uptake

Uptake and toxicity of Ni-Co mixtures in Enchytraeus crypticus were determined after 4 d, 7 d, 10 d, and 14 d exposure. Generally, body concentrations of Ni and Co increased with increasing exposure concentrations. Ni body concentration was significantly reduced in the presence of Co, whereas Ni only marginally affected Co uptake. When expressed as free ion activities, individual toxicity of Ni and Co increased with time, with median lethal concentrations (LC50) decreasing from 78.3 μM and 511 μM at 4 d to 40.4 μM and 393 μM at 14 d, respectively. When expressed as body concentrations, LC50BodyNi remained constant with time whereas LC50BodyCo increased during the first 7 d but remained stable afterwards. As identified by the MIXTOX model, interactions between Ni and Co were mainly antagonistic when based on free ion activities, however, no interaction was observed when based on body concentrations. A process-based model, incorporating exposure time to analyze the mechanisms underlying the dynamic mixture toxicity confirmed the differences in toxicokinetics of the 2 metals. The author's findings suggest that body concentrations, which incorporate bioaccumulation processes, are time-independent and can act as a more constant indicator of metal toxicity. The observed antagonism was mainly caused by competition between Co and Ni for binding sites and subsequent inhibition of Ni uptake. This competitive interaction occurred at the uptake level (toxicokinetics), but not at the target level (toxicodynamics)

Different dynamic accumulation and toxicity of ZnO nanoparticles and ionic Zn in the soil sentinel organism Enchytraeus crypticus

There is still no consensus over the specific effects of metal-based nanoparticles when compared with the conventional metal salts. Here, the accumulation and toxicity of ZnO-NPs and ZnCl2 in Enchytraeus crypticus over time (1–14 d) were investigated using a sand-solution exposure medium and applying a toxicokinetics and toxicodynamics approach. For both Zn forms, body Zn concentration in the organisms was dependent on both the exposure concentration and exposure time, with equilibrium being reached after 7–14 days of exposure. Generally, the uptake and elimination rate constants (Ku and Ke1) were smaller for ZnO-NPs (5.74–12.6 mg kg−1d−1 and 0.17–0.39 d−1) than for ZnCl2 (8.32–40.1 mg kg−1d−1 and 0.31–2.05 d−1), suggesting that ionic Zn was more accessible for E. crypticus than nanoparticulate Zn. Based on external exposure concentrations, LC50s for ZnO-NPs and ZnCl2 decreased with time from 123 to 67 Zn mg L−1 and from 86 to 62 Zn mg L−1, reaching an almost similar ultimate value within 14 d. LC50s based on body Zn concentrations were almost constant over time (except for 1 d) for both ZnO-NPs and ZnCl2, with overall LC50body of Zn being 1720 and 1306 mg kg−1 dry body weight, respectively. Body Zn concentration, which considers all available pathways, was a good predictor of dynamic toxicity of ZnCl2, but not for ZnO-NPs. This may be attributed to the specific internal distribution and detoxification mechanisms of ZnO-NPs. The particles from ZnO-NPs dominated the accumulation (>75%) and toxicity (∼100%). Our results suggest that dynamic aspects should be taken into account when assessing and comparing NPs and metals uptake and consequent patterns of toxicity

Incorporation of chemical and toxicological availability into metal mixture toxicity modeling: State of the art and future perspectives

In the real world, metals are generally present as mixtures, but evaluating their mixture toxicity is still a daunting challenge. The classic conceptual models of concentration addition (CA) and independent action (IA) have been widely used by simply adding doses and responses to predict mixture effects assuming there is non-interaction. In cases where interactions do occur in a mixture, both CA and IA are no longer applicable for quantifying the toxicity, because interpretation of the observed joint effects is often limited to overall antagonism or synergism. In metal mixtures, interactive effects may occur at various levels, such as the exposure level, the uptake level, and the target level. A comprehensive understanding of the mechanisms of joint toxicity is therefore needed to incorporate the interactive effects of mixture components in predicting mixture toxicity. With this in mind, numerous bioavailability-based methods may be considered, with diverse mechanistic perspectives, such as the biotic ligand model (BLM), the electrostatic toxicity model (ETM), the WHAM-F tox approach, a toxicokinetic-toxicodynamic (TK-TD) and an omics-based approach. This review therefore timely summarizes the representative predictive tools and their underlying mechanisms and highlights the importance of integrating mixture interactions and bioavailability in assessing the toxicity and risks of metal mixtures

Interactions of arsenic, copper, and zinc in soil-plant system:Partition, uptake and phytotoxicity

Arsenic, copper, and zinc are common elements found in contaminated soils but little is known about their combined effects on plants when presented simultaneously. Here, we systematically investigated the phytotoxicity and uptake of binary and ternary mixtures of As, Cu, and Zn in a soil-plant system, using wheat (Triticum aestivum) as model species. The reference models of concentration addition (CA) and response addition (RA) coupled with different expressions of exposure (total concentrations in soil ([M]tot, mg/kg), free ion activities in soil solution ({M}, μM), and internal concentrations in plant roots ([M]int, μg/g)), were selected to assess the interaction mechanisms of binary mixtures of As–Cu, As–Zn, and Cu–Zn. Metal(loid) interactions in soil were estimated in terms of solution-solid partitioning, root uptake, and root elongation effects. The partitioning of one metal(loid) between the soil solution and solid phase was most often inhibited by the presence of the other metal(loid). In terms of uptake, inhibitory effects and no effects were observed in the mixtures of As, Cu, and Zn, depending on the mixture combinations and the dose metrics used. In terms of toxicity, simple (antagonistic or synergistic) and more complex (dose ratio-dependent or dose level-dependent) interaction patterns of binary mixtures occurred, depending on the dose metrics selected and the reference models used. For ternary mixtures (As-Cu-Zn), nearly additive effects were observed irrespective of dose descriptors and reference models. The observed interactions in this study may help to understand and predict the joint toxicity of metal(loid)s mixtures in soil-plant system. Mixture interactions and bioavailability should be incorporated into the regulatory framework for accurate risk assessment of multimetal-contaminated sites

Model-based rationalization of mixture toxicity and accumulation in Triticum aestivum upon concurrent exposure to yttrium, lanthanum, and cerium

Rare earth elements (REEs) often co-exist in the environment, but predicting their ‘cocktail effects’ is still challenging, especially for high-order mixtures with more than two components. Here, we systematically investigated the toxicity and accumulation of yttrium, lanthanum, and cerium mixtures in Triticum aestivum following a standardized bioassay. Toxic effects of mixtures were predicted using the reference model of Concentration Addition (CA), Ternary model, and Ternary-Plus model. Interactions between the REEs in binary and ternary mixtures were determined based on external and internal concentrations, and their magnitude estimated from the parameters deviated from CA. Strong antagonistic interactions were found in the ternary mixtures even though there were no significant interactions in the binary mixtures. Predictive ability increased when using the CA model, Ternary model, and Ternary-Plus model, with R2 = 0.78, 0.80, and 0.87 based on external exposure concentrations, and R2 = 0.72, 0.73, and 0.79, respectively based on internal concentrations. The bioavailability-based model WHAM-FTOX explained more than 88 % and 85 % of the toxicity of binary and ternary REE treatments, respectively. Our result showed that the Ternary-Plus model and WHAM-FTOX model are promising tools to account for the interaction of REEs in mixtures and could be used for their risk assessment

Photosynthetic, antioxidative, and metabolic adjustments of a crop plant to elevated levels of La and Ce exposure.

Rare earth elements (REEs) have been widely applied as fertilizers in farmland of China for decades to improve the yield and quality of crops. Unfortunately, adverse effects on plants have been observed due to overdosing with REEs. Until now, the toxicology of REEs was mainly evaluated based on phenotypic responses, but knowledge gaps still exist concerning their metabolic effects. Here, the physiological responses and nontargeted metabolomics studies were combined to systematically explore the potential effects of La and Ce on a crop plant, wheat Triticum aestivum. It was observed that REEs accumulated in the shoots of wheat, with significant reduction of the shoot biomass at higher exposure doses. The disturbance of photosynthesis and induced oxidative stress were identified by analyzing indicators of the photosynthetic (chlorophyll a/b, carotenoid and rubisco) and antioxidant systems (POD, CAT, SOD, GSH and MDA). Furthermore, the global metabolic profiles of REEs treatment groups and the non-exposed control group were screened and compared, and the metabolomic disturbance of REEs was dose-dependent. A high overlap of significantly changed metabolites and matched disturbed biological pathways was found between La and Ce treatments, indicating similarity of their toxicity mechanism in wheat shoots. Generally, the perturbed metabolomic pathways were mainly related to carbohydrate, amino acid and nucleotide/side metabolism, suggesting a disturbance of carbon and nitrogen metabolism, which finally affected the growth of wheat. We thus proved the potential adverse effect of inappropriate application of REEs in crop plants and postulated metabolomics as a feasible tool to identify the underlying toxicological mechanisms.Environmental Biolog

Editorial for the Special Issue “Phytotoxicity of Heavy Metals in Contaminated Soils”

Soil is an essential natural resource because of the ecosystem services it carries out in the terrestrial ecosystem: the provision of food, fibre and fuel; habitats for organisms; nutrient cycling; climate regulation and carbon sequestration; water purification and soil contaminant reductions; and others [...

Impact of nanopesticide CuO-NPs and nanofertilizer CeO2-NPs on wheat Triticum aestivum under global warming scenarios

Concurrent effect of nanomaterials (NMs) and warming on plant performance remains largely unexplored. In this study, the effects of nanopesticide CuO and nanofertilizer CeO2 on wheat (Triticum aestivum) under optimal (22 °C) and suboptimal (30 °C) temperatures were evaluated. CuO-NPs exerted a stronger negative effect on plant root systems than CeO2-NPs at tested exposure levels. The toxicity of both NMs could be attributed to altered nutrient uptake, induced membrane damage, and raised disturbance of antioxidative related biological pathways. Warming significantly inhibited root growth, which was mainly linked to the disturbance of energy metabolism relevant biological pathways. The toxicity of NMs was enhanced upon warming, with a stronger inhibition of root growth and Fe and Mn uptake. Increasing temperature increased the accumulation of Ce upon CeO2-NP exposure, while the accumulation of Cu was not affected. The relative contribution of NMs and warming to their combined effects was evaluated by comparing disturbed biological pathways under single and multiple stressors. CuO-NPs was the dominant factor inducing toxic effects, while both CeO2-NPs and warming contributed to the mixed effect. Our study revealed the importance of carefully considering global warming as a factor in risk assessment of agricultural applications of NMs

Coherent toxicity prediction framework for deciphering the joint effects of rare earth metals (La and Ce) under varied levels of calcium and NTA

9 pages, 3 figures, 2 tablesWith the development of modern technologies, the exploitation and application of rare earth metals (REMs) have increased parallelly. Consequently, more REMs are entering into the environment and therefore there is a pressing need to assess their potential environmental hazards. Here, a standard toxicity test with wheat (Triticum aestivum) was conducted to investigate the single and mixture toxicity of La and Ce in solutions with different levels of calcium and nitrilotriacetic acid (NTA) and results were deciphered by different modeling approaches. Both La and Ce caused adverse effect to wheat, but the presence of Ca and NTA alleviated their toxicity. The obtained EC50 for [La] or [Ce] changed by more than 28-fold and by 4-fold, respectively, with the increase of Ca or NTA. The biotic ligand model (BLM) explained approximately 93% variation of single La or Ce toxicity. The binding constants obtained were 4.14, 6.67, and 6.59 for logKCaBL, logKLaBL, and logKCeBL respectively. The electrostatic toxicity model (ETM) was proved as effective as the BLM, with R2 = 0.93 for La and R2 = 0.92 for Ce. For La–Ce mixtures, parameters from single toxicity approaches were applied successfully to predict the mixture toxicity with concentration addition (CA) model based on the BLM or ETM theory (R2 = 0.92 and RMSE = 8.56; R2 = 0.90 and RMSE = 9.6, respectively). Thus, the results obtained in this study prove that both ETM and BLM theories are appropriate to predict single and mixture REMs toxicity, providing coherent and promising tools for the risk assessment of REM pollutionThis study was supported by the Key Laboratory of Original Agro-Environmental Pollution Prevention and Control, Ministry of Agriculture and Rural Affairs/Tianjin Key Laboratory of Agro-Environment and Agro-Product Safety, Agro-Environment Protection Institution, Ministry of Agriculture and Rural Affairs (No. 17Z1170010019), the National Natural Science Foundation of China (No. 41701573, No. 41701571, No. 41877500, and No. 41977115), the National Key R&D Program of China (No. 2018YFC1800600, No. 2018YFD0800700), and the Research Fund Program of Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology (No. 2018K01Peer reviewe

Subcellular localization and compartment-specific toxicokinetics of cadmium, arsenic, and zinc in brandling worm Eisenia fetida.

Awareness of toxicokinetics at the subcellular level is crucial to deciphering the underlying intoxication processes of metal(loid)s, although this information is often lacking. Here, the toxicokinetics of two non-essential metal(loid)s (Cd and As) and one essential metal (Zn) in both the whole body and subcellular fractions of earthworm (Eisenia fetida) were assessed. Earthworms were exposed to natural soils originating from a gradient of metal(loid) pollution for 14 days followed by a 14-day elimination phase in clean soil. Clearly distinct toxicokinetic patterns were found in the earthworms according to the metal(loid) considered. An obvious concentration-dependent increase was observed in earthworms or subcellular compartments where no equilibrium was reached (with slow or no elimination) for Cd and As throughout the experiment. As for Zn, the earthworms were able to retain a steady-state concentration of Zn in its body or each fraction without a clear intake behavior via the dynamic trade-off between uptake and elimination at different pollution levels. These differences in toxicokinetics at the subcellular level supported the observed differences in bioaccumulation patterns and were indicative of the strategy by which non-essential and essential elements are handled by earthworms. Notably, the concentration of Cd and As in subcellular compartments showed the same pattern as for Zn in the order of cellular cytosol > cellular debris > metal-rich granules, which might be associated with the binding of non-essential/essential elements with metallothionein enriched in the cytosol. Our findings enhance the understanding of the underlying mechanisms for metal(loid) accumulation kinetics in earthworms from the perspective of subcellular partitioning, and will be beneficial for accurate risk assessment of Cd, As, and Zn.Environmental Biolog