Modeling temperature-dependent life-cycle toxicity of thiamethoxam in Chironomus riparius using a DEB-TKTD model.

The neonicotinoid insecticide thiamethoxam (TMX) is widely used to protect crops against insect pests. Despite some desirable properties such as its low toxicity to birds and mammals, concerns have been raised about its toxicity to non-target arthropods, including freshwater insects like chironomids. Whereas multiple studies have investigated chronic effects of neonicotinoids in chironomid larvae at standardized laboratory conditions, a better understanding of their chronic toxicity under variable temperatures and exposure is needed for coherent extrapolation from the laboratory to the field. Here, we developed a quantitative mechanistic effect model for Chironomus riparius, to simulate the species' life history under dynamic temperatures and exposure concentrations of TMX. Laboratory experiments at four different temperatures (12, 15, 20, 23 °C) and TMX concentrations between 4 and 51 µg/L were used to calibrate the model. Observed concentration-dependent effects of TMX in C. riparius included slower growth, later emergence, and higher mortality rates with increasing concentrations. Furthermore, besides a typical accelerating effect on the organisms' growth and development, higher temperatures further increased the effects associated with TMX. With some data-informed modeling decisions, most prominently the inclusion of a size dependence that makes larger animals more sensitive to TMX, the model was parametrized to convincingly reproduce the data. Experiments at both a constant (20 °C) and a dynamically increasing temperature (15-23 °C) with pulsed exposure were used to validate the model. Finally, the model was used to simulate realistic exposure conditions using two reference exposure scenarios measured in Missouri and Nebraska, utilizing a moving time window (MTW) and either a constant temperature (20 °C) or the measured temperature profiles belonging to each respective scenario. Minimum exposure multiplication factors leading to a 10% effect (EP10) in the survival at pupation, i.e., the most sensitive endpoint found in this study, were 25.67 and 21.87 for the Missouri scenario and 38.58 and 44.64 for the Nebraska scenario, when using the respective temperature assumptions. While the results illustrate that the use of real temperature scenarios does not systematically modify the EPx in the same direction (making it either more or less conservative when used as a risk indicator), the advantage of this approach is that it increases the realism and thus reduces the uncertainty associated with the model predictions.

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.

Investigating Population-Level Toxicity of the Antidepressant Citalopram in Harpacticoid Copepods Using In Vivo Methods and Bioenergetics-Based Population Modeling.

Recent research has revealed various lethal and sublethal effects of the selective serotonin reuptake inhibitor citalopram hydrobromide on the harpacticoid copepod Nitocra spinipes. In the present study, an individual-based model (IBM) grounded in the dynamic energy budget (DEB) theory was developed to extrapolate said effects to the population level. Using a generic DEB-IBM as a template, the model was designed to be as simple as possible, keeping model components that are outside the scope of the core DEB theory to a minimum. To test the model, a 56-day population experiment was performed at 0, 100, and 1000 µg citalopram hydrobromide L-1 . In the experiment, the populations quickly reached a plateau in the control and at 100 µg L-1 , which was correctly reproduced by the model and could be explained by food limitations hindering further population growth. At 1000 µg L-1 , a clear mismatch occurred: Whereas in the experiment the population size increased beyond the supposed (food competition-induced) capacity, the model predicted a suppression of the population size. It is assumed that the IBM still misses important components addressing population density-regulating processes. Particularly crowding effects may have played an important role in the population experiment and should be further investigated to improve the model. Overall, the current DEB IBM for N. spinipes should be seen as a promising starting point for bioenergetics-based copepod population modeling, which-with further improvements-may become a valuable individual-to-population extrapolation tool in the future. Environ Toxicol Chem 2023;42:1094-1108. © 2023 SETAC.

Making Sense of Life-History Effects of the Antidepressant Citalopram in the Copepod Nitocra spinipes Using a Bioenergetics Model.

The global consumption of human antidepressants has steadily increased over the last years. The most widely prescribed antidepressants are the selective serotonin reuptake inhibitors (SSRIs), which have been linked to various life-history effects in nontarget organisms. We investigated the effects of the SSRI citalopram hydrobromide on the life history of the copepod Nitocra spinipes. Slight but significant developmental delay effects were observed at nominal concentrations of 0.1 and 1 µg/L, with stronger effects occurring at measured concentrations of 178 µg/L and above. At 77 µg/L and above, a significant increase in adult body length and offspring production/brood was found, although the time between brood releases remained unaffected. The pre-adult surviving fraction was significantly reduced (by 44%) at 765 µg/L. For a mechanistic evaluation of these observations, we used a bioenergetics model for N. spinipes based on the dynamic energy budget theory. Toxicokinetic and toxicodynamic submodels were used to dynamically simulate the chemical uptake and elimination, as well as dose-response relationships for hypothetical physiological modes of action and survival over time. Although none of the commonly invoked physiological modes of action, acting on assimilation, maintenance, growth, or offspring production, could explain the observed combination of effects, a newly proposed physiological mode of action acting on the process of maturation delivered correct predictions in terms of each effect's direction. The model fits could be further improved by allowing for a gentler concentration-effect slope and by adding an auxiliary physiological mode of action acting on the reproduction efficiency. The quantitative explanations provided in the present study offer a starting point for exploratory simulation studies investigating the effects of SSRIs at higher ecological levels. Environ Toxicol Chem 2021;40:1928-1939. © 2021 SETAC.

SETAC GLB and SETAC Europe SAC: a liaison promoting the next generation of ecotoxicologists and environmental chemists.

This commentary is an introduction for students to the Society of Environmental Toxicology and Chemistry (SETAC) and its Student Advisory Council (SAC). As young academics face challenges while trying to develop their careers, SETAC and the SAC help facilitate student involvement in the various communities within the society that can help to develop the students' careers within the environmental sciences [e.g. the German Language Branch (GLB)]. This piece would also like to emphasize and pay homage to the continual cooperation between the SAC and the ESEU, which provides a scientific platform to communicate internationally and beyond the borders of SETAC, as well as offer heartfelt congratulations from the SAC to the GLB for their "20 Years SETAC GLB" and deep gratitude for their strong advocacy and support of the SAC.

Temperature and food quantity effects on the harpacticoid copepod Nitocra spinipes: Combining in vivo bioassays with population modeling.

The harpacticoid copepod Nitocra spinipes has become a popular model species for toxicity testing over the past few decades. However, the combined influence of temperature and food shortage, two climate change-related stressors, has never been assessed in this species. Consequently, effects of three temperatures (15, 20 and 25°C) and six food regimes (between 0 and 5 × 105 algal cells/mL) on the life cycle of N. spinipes were examined in this study. Similarly to other copepod species, development times and brood sizes decreased with rising temperatures. Mortality was lowest in the 20°C temperature setup, indicating a close-by temperature optimum for this species. Decreasing food concentrations led to increased development times, higher mortality and a reduction in brood size. A sex ratio shift toward more females per male was observed for increasing temperatures, while no significant relationship with food concentration was found. Temperature and food functions for each endpoint were integrated into an existing individual-based population model for N. spinipes which in the future may serve as an extrapolation tool in environmental risk assessment. The model was able to accurately reproduce the experimental data in subsequent verification simulations. We suggest that temperature, food shortage, and potentially other climate change-related stressors should be considered in environmental risk assessment of chemicals to account for non-optimal exposure conditions that may occur in the field. Furthermore, we advocate combining in vivo bioassays with population modeling as a cost effective higher tier approach to assess such considerations.

Yangtze Three Gorges Reservoir, China: A holistic assessment of organic pollution, mutagenic effects of sediments and genotoxic impacts on fish.

Besides obvious benefits, the Three Gorges Dam's construction resulted in new pollution scenarios with the potentials to threaten the Three Gorges Reservoir (TGR) ecosystem. In order to record organic contamination, to find links to ecotoxicological impacts and to serve as reference for ensuing monitoring, several sites in the TGR area were screened applying the triad approach with additional lines-of-evidence as a holistic assessment method. Sediments and the benthic fish species Pelteobagrus vachellii were sampled in 2011 and 2012 to determine organic pollution levels, mutagenic potentials and genotoxic impacts. Two regional hot-spots near the cities of Chongqing and Kaixian were identified and further investigated in 2013. Only polycyclic aromatic hydrocarbons (PAHs) could be detected in sediments in 2011 (165-1653ng/g), emphasizing their roles as key pollutants of the area. Their ubiquity was confirmed at Chongqing (150-433ng/g) and Kaixian (127-590ng/g) in 2013. Concentrations were comparable to other major Chinese and German rivers. However, the immense sediment influx suggested a deposition of 216-636kgPAH/day (0.2-0.6mgPAH/(m(2)·day)), indicating an ecotoxicological risk. PAH source analysis highlighted primary impacts of combustion sources on the more industrialized upper TGR section, whereas petrogenic sources dominated the mid-low section. Furthermore, sediment extracts from several sites exhibited significant activities of frameshift promutagens in the Ames fluctuation assay. Additionally, significant genotoxic impairments in erythrocytes of P. vachellii were detected (Chongqing/Kaixian), demonstrating the relevance of genotoxicity as an important mode of action in the TGR's fish. PAHs, their derivatives and non-target compounds are considered as main causative agents.

Malformation of the vomer in submucous cleft palate.

Background: Several criteria are described in the literature to diagnose a submucous cleft palate. Commonly the differences in the extent of the submucous cleft will not be as overt as in open clefts. Nevertheless, complete submucous cleft palate may cause imperfect palato-pharyngeal closure so that the affected person needs to undergo speech training and surgical treatment. Patients: We investigated 30 patients who underwent palatal repair to correct this disorder. They were evaluated according to the Koch's documentation system. Results: In all patients an additional malformation of the inner nose was found: The vomer was not fused with the palatal shelves. There were with different degrees of severity of this malformation and they were not necessarily correlated with the extent of the palatal cleft. Conclusion: In our opinion, this malformation of the vomer should be seen as a typical symptom of classical submucous cleft palate. Discussion is needed on how the vomerine malformation should be incorporated into the surgical procedure. Since we know from septal surgery that a basal septal perforation will lead to disturbances of nasal breathing. Copyright 2001 European Association for Cranio-Maxillofacial Surgery.