Physiological Mode Of Action Research Articles

Advancing Soil Risk Assessment: A Novel Earthworm Cocoon Test with a Complementary Toxicokinetic-Toxicodynamic Modeling Approach.

In the current European Union pesticide risk assessment for soil organisms, effect endpoints from laboratory studies (Tier 1) and field studies (higher-tier risk assessment) are compared with predicted environmental concentrations in soil, derived from the proposed use pattern. The simple but conservative initial Tier 1 risk assessment considers a range of worst-case assumptions. In contrast, the higher-tier assessment focuses on specific conditions tested in the corresponding field study. Effect modeling, such as toxicokinetic-toxicodynamic (TKTD) modeling, is considered a promising future tool to address uncertainties in soil risk assessment, such as extrapolation to different ecological, pedo-climatical, or agronomical situations, or to serve as an intermediate tier for potential refinement of the risk assessment. For the implementation of TKTD modeling in soil organism risk assessment, data on earthworm growth and reproduction over time are required, which are not provided by the standard Organisation for Economic Co-operation and Development (OECD) 222 laboratory test. The underlying study with carbendazim presents a new earthworm cocoon test design, based on the OECD 222 test, to provide the necessary data as input for TKTD modeling. This proposed test design involves destructive samplings at days 7, 14, 21, and 28, enabling the determination of growth, cocoon number, and the number of juveniles hatched per cocoon in 7-day intervals. The new cocoon test allowed the disentanglement of the toxic effect of carbendazim in earthworms: At the highest concentration prominent effects on growth and reproductive output were observed, and the number of cocoons was significantly reduced compared to control. The results highlighted different physiological modes of action: effect on growth via higher maintenance costs as a primary mode of action as well as a reduced number of cocoons (effect on reproduction) and a lower number of juveniles hatching from each cocoon (hazard during oogenesis) as a secondary mode of action. We provide an example of how this new test's data can be used to feed a dynamic energy budget theory-TKTD model of Eisenia fetida. We also validate it against the original OECD 222 test design, outlining its potential future use in soil risk assessment. Environ Toxicol Chem 2024;43:2377-2386. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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.

Sublethal effects of binary mixtures of Cu2+ and Cd2+ on Daphnia magna: Standard Dynamic Energy Budget (DEB) model analysis

Dynamic Energy Budget theory (DEB) describes mass and energy fluxes that occur in living organisms. DEB models were successfully used to assess the influence of stress, including toxic substances, and changes in pH and temperature, on different organisms. In this study, the Standard DEB model was used to evaluate the toxicity of copper and cadmium ions and their binary mixtures on Daphnia magna. Both metal ions have a significant influence on daphnia growth and reproduction. Different physiological modes of action (pMoA) were applied to primary DEB model parameters. Model predictions for chosen modes of interaction of mixture components were evaluated. The goodness of model fit and the model prediction was assessed to indicate the most likely pMoA and interaction mode. Copper and cadmium influence more than one DEB model primary parameter. Different pMoAs can result in similar model fits, and therefore it is difficult to identify pMoA only by evaluation of the goodness of fit of the model to the growth and reproduction data. Some critical discussion and ideas for model development are therefore provided.

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.

Predicting Combined Effects of Chemical Stressors: Population-Level Effects of Organic Chemical Mixtures with a Dynamic Energy Budget Individual-Based Model.

Most regulatory ecological risk-assessment frameworks largely disregard discrepancies between the laboratory, where effects of single substances are assessed on individual organisms, and the real environment, where organisms live together in populations and are often exposed to multiple simultaneously occurring substances. We assessed the capability of individual-based models (IBMs) with a foundation in the dynamic energy budget (DEB) theory to predict combined effects of chemical mixtures on populations when they are calibrated on toxicity data of single substances at the individual level only. We calibrated a DEB-IBM for Daphnia magna for four compounds (pyrene, dicofol, α-hexachlorocyclohexane, and endosulfan), covering different physiological modes of action. We then performed a 17-week population experiment with D. magna (designed using the DEB-IBM), in which we tested mixture combinations of these chemicals at relevant concentrations, in a constant exposure phase (7-week exposure and recovery), followed by a pulsed exposure phase (3-day pulse exposure and recovery). The DEB-IBM was validated by comparing blind predictions of mixture toxicity effects with the population data. The DEB-IBM accurately predicted mixture toxicity effects on population abundance in both phases when assuming independent action at the effect mechanism level. The population recovery after the constant exposure was well predicted, but recovery after the pulse was not. The latter could be related to insufficient consideration of stochasticity in experimental design, model implementation, or both. Importantly, the mechanistic DEB-IBM performed better than conventional statistical mixture assessment methods. We conclude that the DEB-IBM, calibrated using only single-substance individual-level toxicity data, produces accurate predictions of population-level mixture effects and can therefore provide meaningful contributions to ecological risk assessment of environmentally realistic mixture exposure scenarios. Environ Toxicol Chem 2022;41:2240-2258. © 2022 SETAC.

Design, synthesis, and biological evaluation of chalcones for anticancer properties targeting glycogen synthase kinase 3 beta

Chalcones compounds have been investigated to exhibit anticancer activity through various physiological modes of action. In order to develop chalcone compounds with novel anticancer-related modes of action, diverse chalcone compounds were designed and synthesized. Variously substituted poly-methoxy chalcone compounds 1–17 were prepared, and their structures were identified using high-resolution mass spectrometry (HR/MS) and nuclear magnetic resonance (NMR) experiments. Long-term survival clonogenic assay was applied to evaluate their anti-cancer abilities and revealed that their GI50 values ranged between 1.33 and 172.20 μM. When MCF-7SC cells were treated with various concentrations of compound 14, reduced cell viability and induced apoptosis in MCF-7SC cells were observed in a dose-dependent manner. Wound healing assay demonstrated that compound 14 prevented the MCF7-SC migrated cells at non-lethal concentrations after 12 and 24 h of exposure. The efficiency of compound 14 on the levels of Epithelial-mesenchymal transition (EMT) markers was accessed by the western blot analysis. For the concrete understanding of anticancer properties at the molecular level, in vitro kinase assays on 12 cancer related proteins were carried out. Glycogen synthase kinase 3 beta (GSK3β) was most effectively inhibited by compound 14 with 89% inhibitory activity at 10 µM against GSK3β. The binding mode of compound 14 with GSK3β was reinforced through in silico experiments, which demonstrated compound 14 binds with GSK3β at binding affinity ranged between − 7.5 kcal/mol and − 6.8 kcal/mol. SwissADME analysis provided the druggability and leadlikeness of compound 14, which unveiled drug development possibilities of chalcone compound 14.

Population modeling to inform management and recovery efforts for lake sturgeon, Acipenser fulvescens.

Lake sturgeon (Acipenser fulvescens) populations have significantly declined across their historic range, in large part due to anthropogenic impacts that have likely been exacerbated by the life-history traits of this slow-growing and long-lived species. We developed a population model to explore how Contaminants of Emerging Concern (CECs) impact lake sturgeon populations. We explored how different physiological modes of action (pMoAs) of CECs impacted population abundance and recovery and how different simulated management actions could enable recovery. We first estimated the impacts on population abundance and recovery by comparing the trajectory of an unexposed population to a population that had been exposed to a CEC with a specific pMoA after the end of the exposure. We then predicted how different management actions would impact population recovery by comparing the trajectories of an unexposed population to an exposed population for which a management action started at a fixed time without discontinuation of the exposure. Our results predicted that the individual-level pMoA of CECs has an important impact on population-level effects because different stressor's pMoA impacts the life-history traits of sturgeon differently. For example, the feeding and reproduction pMoAs caused the strongest and weakest population declines, respectively. For the same reason, pMoA also impacted recovery. For example, recovery was delayed when the pMoA was growth, maintenance, or feeding, but it was immediate when the pMoA was reproduction. We found that management actions that increased the egg survival rate or the stocking of fingerlings resulted in faster and stronger recovery than management actions that increased the juvenile or adult survival rate. This result occurred because the first two management actions immediately impacted recruitment, whereas the impact was delayed for the last two. Finally, there was greater potential for recovery when management action targeted eggs and fingerlings because these life stages have lower natural survival rates. Integr Environ Assess Manag 2022;18:1597-1608. © 2022 Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Theta-modulated oscillatory transcranial direct current stimulation over posterior parietal cortex improves associative memory

Associative memory (AM) reflects the ability to remember and retrieve multiple pieces of information bound together thus enabling complex episodic experiences. Despite growing interest in the use of transcranial direct current stimulation (tDCS) for the modulation of AM, there are inconsistent evidence regarding its benefits. An alternative to standard constant tDCS could be the application of frequency-modulated tDCS protocols, that mimic natural function-relevant brain rhythms. Here, we show the effects of anodal tDCS oscillating in theta rhythm (5 Hz; 1.5 ± 0.1 mA) versus constant anodal tDCS and sham over left posterior parietal cortex on cued recall of face-word associations. In a crossover design, each participant completed AM assessment immediately following 20-min theta-oscillatory, constant, and sham tDCS, as well as 1 and 5 days after. Theta oscillatory tDCS increased initial AM performance in comparison to sham, and so did constant tDCS. On the group level, no differences between oscillatory and constant tDCS were observed, but individual-level analysis revealed that some participants responded to theta-oscillatory but not to constant tDCS, and vice versa, which could be attributed to their different physiological modes of action. This study shows the potential of oscillatory tDCS protocols for memory enhancement to produce strong and reliable memory-modulating effects which deserve to be investigated further.

DEB-tox and Data Gaps: Consequences for individual-level outputs

In this paper, we analyze the impact of data gaps in the context of ecotoxicology when parameterizing a species using a widely recognized theory, the Dynamic Energy Budget (DEB) theory. DEB-based models are used in many ecological domains, and have been recognized as particularly useful in ecotoxicology. However, available datasets are often insufficient to accurately estimate all model parameters.We utilized a data-rich, parameterized species that is widely used in laboratory tests, Danio rerio (zebrafish). We compared two versions (“old” and “new”) of DEB parametrization methods when (i) removing datasets one-by-one, to understand if one dataset was particularly relevant for parameter estimation; and (ii) removing datasets cumulatively, to test how many datasets were necessary to achieve a meaningful parametrization. Using the results of the newer version of the parametrization routine, we checked how differences in parameter estimations could affect the modeled length and egg production of zebrafish. Finally, we assessed the relevance of these differences in an ecotoxicological context. For this purpose, we applied five hypothetical stressors, with different Physiological Modes of Action, to understand the impact of data gaps on estimating stressor effects on individual fish length and egg production.Our work shows that the new parametrization method is robust and efficient even when used with the minimum amount of data suggested by DEB theory. The parameters that are affected the most by data gaps are the maturity threshold parameters. At the individual level, data gaps affect mostly egg production. However, the link between data gaps and individual egg production is not always straightforward. Stressor effects can amplify or decrease differences between data-rich and data-poor scenarios, but usually their effects are consistent within each scenario, confirming DEB models as a powerful tool in ecological and ecotoxicological studies. We suggest careful consideration of the potential effects of data gaps when implementing DEB-based population models.

Physiological modes of action across species and toxicants: the key to predictive ecotoxicology.

As ecotoxicologists we strive for a better understanding of how chemicals affect our environment. Humanity needs tools to identify those combinations of man-made chemicals and organisms most likely to cause problems. In other words: which of the millions of species are at risk from pollution? And which of the tens of thousands of chemicals contribute most to the risk? We identified our poor knowledge on physiological modes of action (how a chemical affects the energy allocation in an organism), and how they vary across species and toxicants, as a major knowledge gap. We also find that the key to predictive ecotoxicology is the systematic, rigorous characterization of physiological modes of action because that will enable more powerful in vitro to in vivo toxicity extrapolation and in silico ecotoxicology. In the near future, we expect a step change in our ability to study physiological modes of action by improved, and partially automated, experimental methods. Once we have populated the matrix of species and toxicants with sufficient physiological mode of action data we can look for patterns, and from those patterns infer general rules, theory and models.

Dysferlin mediates membrane tubulation and links T-tubule biogenesis to muscular dystrophy.

The multi-C2 domain protein dysferlin localizes to the plasma membrane and the T-tubule system in skeletal muscle; however, its physiological mode of action is unknown. Mutations in the DYSF gene lead to autosomal recessive limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Here, we show that dysferlin has membrane tubulating capacity and that it shapes the T-tubule system. Dysferlin tubulates liposomes, generates a T-tubule-like membrane system in non-muscle cells, and links the recruitment of phosphatidylinositol 4,5-bisphosphate to the biogenesis of the T-tubule system. Pathogenic mutant forms interfere with all of these functions, indicating that muscular wasting and dystrophy are caused by the dysferlin mutants' inability to form a functional T-tubule membrane system.

Genetic and genomic dissection of Prolactin revealed potential association with milk production traits in riverine buffalo.

Milk yield and quality has been a major selection criterion for genetic improvement in livestock species. Role of Prolactin gene in determining milk quality in terms of protein profile, lactose, lipids and other imperative macromolecules is very important. In this context, genetic profiling of Prolactin gene in riverine buffalo of Pakistan was performed and potential genetic markers were identified illustrating worth of this gene in marker-assisted selection of superior dairy buffaloes. Series of wet and dry lab experimentation was performed starting with genomic DNA isolation from true to breed representatives of indigenous river buffalo (Nili-Ravi). After amplification of coding regions of Prolactin gene, products were eluted and sequenced by Sanger's chain termination method and aligned to get variations in genomic region. A total of 15 novel variations were identified and analyzed statistically for their significance at population level, haplotypes were constructed, and association was estimated. Phylogenetic analysis was performed to evaluate the rate of evolution for Prolactin gene in various mammalian species. Lastly, biological networking for this molecule was predicted to get the bigger pictorial of its functional machinery. Pathway analysis was performed to find its physiological mode of action in milk synthesis. This is a first report toward complete genetic screening of Prolactin gene in Pakistani buffaloes. Results of this study not only provide an insight for potential role of Prolactin gene in milk-producing abilities of buffalo but also suggest new directions for exploration of more genes that may have promising role to enhance future milk production capabilities of river buffalo breeds of Asian region through marker-assisted selection.

Fermented and extruded wheat bran in piglet diets: impact on performance, intestinal morphology, microbial metabolites in chyme and blood lipid radicals

The aim of the present study was to evaluate the influence of native, fermented and extruded wheat bran on the performance and intestinal morphology of piglets. Additionally, short-chain fatty acids (SCFA), biogenic amines, ammonia, lactic acid, pH as well as E. coli and lactic acid bacterial counts were analysed in digesta samples from three gut sections. Furthermore, the antioxidant potential in blood samples was evaluated based on the lipid radicals formed. For this purpose, 48 newly weaned piglets (28 d old) were allocated to one of the four different dietary treatment groups: no wheat bran (Control), native wheat bran, fermented wheat bran as well as extruded wheat bran. Wheat bran variants were included at 150 g/kg into the diets. All diets were mixed to reach the calculated isonitrogenic nutrient contents. Gut tissue and digesta samples were collected from the proximal jejunum, the terminal ileum and the colon ascendens, blood samples directly at slaughter. Although none of the dietary interventions had an impact on performance parameters, the amount of goblet cells in the ileum was increased upon feeding native and extruded wheat bran, compared to fermented bran (p < 0.05). The E. coli counts in colonic chyme were significantly lower (p < 0.05) in the Control group compared to the groups fed with wheat bran. The concentration of SCFA showed differences for minor compounds (p < 0.05), while linear contrast analyses revealed a reduced concentration of total SCFA in the colon following the feeding of modified wheat bran compared to native wheat bran. This may suggest that several compounds are more easily digested already in the ileum, resulting in a reduced nutrient flow into the large intestine and therefore less unexploited digesta is available as substrate for the microorganisms there. Fermentation also resulted in a significant decrease of methylamine in the colon (p < 0.05), while other biogenic amines in the ileum and colon showed no statistically significant differences. The formation of lipid radicals was decreased (p < 0.05) after feeding native wheat bran compared to the Control group. These results suggest that fermentation and extrusion of wheat bran exert some different impact regarding their physiological mode of action.

Proposed physiological mode of action of rice hemopexin fold protein OsHFP: linking heme-binding with plant cell death

The biosynthetic pathway of tetrapyrrole is under stringent regulation in living systems. Heme, one of the products of this branched pathway is well known to regulate the pathway through feedback inhibition. Since the accumulation of intermediates of tetrapyrrole biosynthetic pathway is found to be cytotoxic and inducer of plant programmed cell death through retrograde signalling, certain role of heme in regulating plant cell death is quite logical. In the present study, we report the in vivo heme-binding property of OsHFP, a novel hemopexin fold protein from the rice (Oryza sativa) plant, and document the effect of heme–OsHFP interaction on oxidative stress responses in bacterial and plant systems. The bound heme is retained by the OsHFP even in presence of SDS, and the amount of bound heme to OsHFP increases upon exogenous application of heme biosynthetic precursor in Escherichia coli. In heme-replete condition, the recombinant OsHFP alters the oxidative stress response in E. coli. Ectopic expression of the OsHFP generates oxidative stress in tobacco leaves, which is visualized through the induction of superoxide dismutase activity and localized accumulation of H2O2. On the basis of the findings from the present study and the available literature, we propose a possible mode of action of OsHFP in regulating cell death in plant system, which might signify the yet-to-be-deciphered physiological role of hemopexin fold proteins in plants.

Limitations of extrapolating toxic effects on reproduction to the population level.

For the ecological risk assessment of toxic chemicals, standardized tests on individuals are often used as proxies for population-level effects. Here, we address the utility of one commonly used metric, reproductive output, as a proxy for population-level effects. Because reproduction integrates the outcome of many interacting processes (e.g., feeding, growth, allocation of energy to reproduction), the observed toxic effects in a reproduction test could be due to stress on one of many processes. Although this makes reproduction a robust endpoint for detecting stress, it may mask important population-level consequences if the different physiological processes stress affects are associated with different feedback mechanisms at the population level. We therefore evaluated how an observed reduction in reproduction found in a standard reproduction test translates to effects at the population level if it is caused by hypothetical toxicants affecting different physiological processes (physiological modes of action; PMoA). For this we used two consumer–resource models: the Yodzis-Innes (YI) model, which is mathematically tractable, but requires strong assumptions of energetic equivalence among individuals as they progress through ontogeny, and an individual-based implementation of dynamic energy budget theory (DEB-IBM), which relaxes these assumptions at the expense of tractability. We identified two important feedback mechanisms controlling the link between individual- and population-level stress in the YI model. These mechanisms turned out to also be important for interpreting some of the individual-based model results; for two PMoAs, they determined the population response to stress in both models. In contrast, others stress types involved more complex feedbacks, because they asymmetrically stressed the production efficiency of reproduction and somatic growth. The feedbacks associated with different PMoAs drastically altered the link between individual- and population-level effects. For example, hypothetical stressors with different PMoAs that had equal effects on reproduction had effects ranging from a negligible decline in biomass to population extinction. Thus, reproduction tests alone are of little use for extrapolating toxicity to the population level, but we showed that the ecological relevance of standard tests could easily be improved if growth is measured along with reproduction.

TNFα inhibitors restrict T cell activation and cycling via Notch-1 signalling in inflammatory bowel disease

BackgroundTumour necrosis factor α (TNFα) inhibitors such as adalimumab and infliximab are frequently prescribed for inflammatory bowel disease (IBD). Despite the clinical success of TNFα inhibitors, their physiological mode of...

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans

BackgroundPhysiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to three toxic chemicals: cadmium, fluoranthene (FA) and atrazine (AZ).ResultsFor Cd, the physiological mode of action as indicated by DEBtox model fitting was an effect on energy assimilation from food, suggesting that the transcriptional response to exposure should be dominated by changes in the expression of transcripts associated with energy metabolism and the mitochondria. While evidence for effect on genes associated with energy production were seen, an ontological analysis also indicated an effect of Cd exposure on DNA integrity and transcriptional activity. DEBtox modelling showed an effect of FA on costs for growth and reproduction (i.e. for production of new and differentiated biomass). The microarray analysis supported this effect, showing an effect of FA on protein integrity and turnover that would be expected to have consequences for rates of somatic growth. For AZ, the physiological mode of action predicted by DEBtox was increased cost for maintenance. The transcriptional analysis demonstrated that this increase resulted from effects on DNA integrity as indicated by changes in the expression of genes chromosomal repair.ConclusionsOur results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes.

Algal testing of titanium dioxide nanoparticles—Testing considerations, inhibitory effects and modification of cadmium bioavailability

The ecotoxicity of three different sizes of titanium dioxide (TiO 2) particles (primary particles sizes: 10, 30, and 300 nm) to the freshwater green alga Pseudokirchneriella subcapitata was investigated in this study. Algal growth inhibition was found for all three particle types, but the physiological mode of action is not yet clear. It was possible to establish a concentration/dose–response relationship for the three particle sizes. Reproducibility, however, was affected by concentration-dependent aggregation of the nanoparticles, subsequent sedimentation, and possible attachment to vessel surfaces. It is also believed that heteroaggregation, driven by algal exopolymeric exudates, is occurring and could influence the concentration–response relationship. The ecotoxicity of cadmium to algae was investigated both in the presence and absence of 2 mg/L TiO 2. The presence of TiO 2 in algal tests reduced the observed toxicity due to decreased bioavailability of cadmium resulting from sorption/complexation of Cd 2+ ions to the TiO 2 surface. However, for the 30 nm TiO 2 nanoparticles, the observed growth inhibition was greater than what could be explained by the concentration of dissolved Cd(II) species, indicating a possible carrier effect, or combined toxic effect of TiO 2 nanoparticles and cadmium. These results emphasize the importance of systematic studies of nanoecotoxicological effects of different sizes of nanoparticles and underline the fact that, in addition to particle toxicity, potential interactions with existing environmental contaminants are also of crucial importance in assessing the potential environmental risks of nanoparticles.

Assessing the Chemical Sensitivity of Freshwater Fish Commonly Used in Toxicological Studies

Abstract Using information from published studies, the relative sensitivity of various freshwater fish to a range of chemicals was examined. Specifically, the objectives were to: (1) determine which species are used most often in toxicity tests, (2) assess the relative sensitivity of these species to various chemicals, and (3) determine whether the two most commonly tested species exhibit differences in their relative sensitivity to different classes of chemicals. Fathead minnows, rainbow trout and bluegill sunfish were the three most commonly used species in 96-h LC50 tests. Of the nine species examined, coho salmon and rainbow trout were the most sensitive species to 190 chemicals, while goldfish and carp were the least sensitive. Fathead minnows and rainbow trout were not equally sensitive to 13 different classes of chemicals; for example, while trout were significantly more sensitive to metals, fathead minnows were more sensitive to hydrocarbons. Such comparisons are expected to be useful for predicting the relative responses of different species to previously untested chemicals in such groups, and in gaining insight into physiological modes of action.

What it takes to get a herbicide's mode of action. Physionomics, a classical approach in a new complexion

Discovering new herbicides with novel modes of action is a priority assignment in plant protection research. However, for active compounds identified in greenhouse screens, the crucial point is to tread the most efficient path in determining a herbicide's target site, regarding chance of success, time and research costs. Today, in the literature, molecular (functional genomics, transcriptomics), biochemical (proteomics) and analytical (metabolomics) approaches are particularly discussed. So far, less attention has been focused on the comprehensive physiological profiling of the complex plant system as a procedure which enables new herbicides, with an unknown target site for their mode of action, to be screened rapidly. Here, the concept of an array of 'functional' bioassays is presented which has ultimately been developed from the classical tool of mode of action diagnosis by symptoms. These bioassays are designed to differentiate between the distinct responses of the multiple organization units (plant, tissue, meristematic cell, organelle), developmental stages, types of metabolism (phototrophic, heterotrophic) and physiological processes in the plant organism. The response pattern to a herbicide can be viewed as the end result of changes induced in the molecular and biochemical process chain and should be diagnostic of its physiological mode of action. The results can be interpreted directly or a fingerprint database for all known modes of action to be screened for analogy. The term 'physionomics' is proposed for this comprehensive physiological profiling of the plant system, following the parallel terminology of the molecular and biochemical 'omics' technologies. Physionomics procedures provide a first clue to the mode of action of a new herbicide that can direct more time-consuming and costly molecular, biochemical, histochemical or analytical studies to identify a target site more efficiently.