Species Differences In Sensitivity Research Articles

Systemic review of the Species Sensitivity Distribution Curve (CDSE) in environmental matrixes: a scientific contribution to ecotoxicological analysis

In ecotoxicity, differences in species sensitivity can be expressed through a curve based on the distribution of pre-existing contaminant toxicity data, enabling better comparative visualization and the deduction of taxonomic groups more and less sensitive to toxic agentes. The objective of this work was to carry out, in a structured way, an investigation in the literature about the application of the species sensitivity distribution (SSD) curve in ecotoxicological analyzes of environmental matrices. To assist in this process of knowledge construction, an adaptation of the intervention instrument ProKnow-C was used, in order to select relevant articles and identify the characteristics of these publications that will scientifically contribute to the theme in question. The main results are the identification of quantitative data for the year of publication, countries and most relevant journals aligned with the proposed theme, the minimum number of data for the construction of the curve and its main applications, as well as identifying gaps for new scientific research, thus contributing to the more precise application of the SDS curve in ecotoxicological analyses.

Characterization of a human thyroid microtissue model for testing thyroid disrupting chemicals.

Perturbation of thyroid hormone (T4) synthesis is known to cause numerous developmental, metabolic, and cognitive disorders in humans. Due to species differences in sensitivity to chemical exposures, there is a need for human-based in vitro approaches that recapitulate thyroid cellular architecture and T4 production when screening. To address these limitations, primary human thyrocytes, isolated from healthy adult donor tissues and cryopreserved at passage one (p'1) were characterized for cellular composition, 3D follicular architecture, and thyroglobulin (TG)/T4 expression and inhibition by prototype thyroid disrupting chemicals (TDC). Flow analysis of the post-thaw cell suspension showed >80% EpCAM-positive cells with 10%-50% CD90-positive cells. When seeded onto 96-well Matrigel®-coated plates and treated with bovine thyroid stimulating hormone (TSH), thyrocytes formed 3D microtissues during the initial 4-5 days of culture. The microtissues exhibited a stable morphology and size over a 14-day culture period. TG and T4 production were highest in microtissues when the proportion of CD90-positive cells, seeding density and thyroid stimulating hormone concentrations were between 10%-30%, 6K-12Kcells per well, and 0.03-1 mIU/mL, respectively. At maximal TG and T4 production levels, average microtissue diameters ranged between 50 and 200µm. The T4 IC50 values for two prototype TPO inhibitors, 6-propyl-2-thiouracil and methimazole, were ∼0.7µM and ∼0.5 µM, respectively, in microtissue cultures treated between days 9 and 14. Overall, p'1 cryopreserved primary human thyrocytes in 3D microtissue culture represent a promising new model system to prioritize potential TDC acting directly on the thyroid as part of a weight-of-evidence hazard characterization.

Comparing Sensitivity of Different Bee Species to Pesticides: A TKTD modeling approach.

Risk assessment for bees is mainly based on data for honey bees; however, risk assessment is intended to protect all bee species. This raises the question of whether data for honey bees are a good proxy for other bee species. This issue is not new and has resulted in several publications in which the sensitivity of bee species is compared based on the values of the 48-h median lethal dose (LD50) from acute test results. When this approach is used, observed differences in sensitivity may result both from differences in kinetics and from inherent differences in species sensitivity. In addition, the physiology of the bee, like its overall size, the size of the honey stomach (for acute oral tests), and the physical appearance (for acute contact tests) also influences the sensitivity of the bee. The recently introduced Toxicokinetic-Toxicodynamic (TKTD) model that was developed for the interpretation of honey bee tests (Bee General Uniform Threshold Model for Survival [BeeGUTS]) could integrate the results of acute oral tests, acute contact tests, and chronic tests within one consistent framework. We show that the BeeGUTS model can be calibrated and validated for other bee species and also that the honey bee is among the more sensitive bee species. In addition, we found that differences in sensitivity between species are smaller than previously published comparisons based on 48-h LD50 values. The time-dependency of the LD50 and the specifics of the bee physiology are the main causes of the wider variation found in the published literature. Environ Toxicol Chem 2024;43:1431-1441. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Hepatic Transcriptomic Responses to Ethinylestradiol in Embryonic Japanese Quail and Double-Crested Cormorant.

Understanding species differences in sensitivity to toxicants is a critical issue in ecotoxicology. We recently established that double-crested cormorant (DCCO) embryos are more sensitive than Japanese quail (JQ) to the developmental effects of ethinylestradiol (EE2). We explored how this difference in sensitivity between species is reflected at a transcriptomic level. The EE2 was dissolved in dimethyl sulfoxide and injected into the air cell of eggs prior to incubation at nominal concentrations of 0, 3.33, and 33.3 µg/g egg weight. At midincubation (JQ 9 days; DCCO 16 days), livers were collected from five embryos/treatment group for RNA sequencing. Data were processed and analyzed using EcoOmicsAnalyst and ExpressAnalyst. The EE2 exposure dysregulated 238 and 1,987 genes in JQ and DCCO, respectively, with 78 genes in common between the two species. These included classic biomarkers of estrogen exposure such as vitellogenin and apovitellenin. We also report DCCO-specific dysregulation of Phase I/II enzyme-coding genes and species-specific transcriptional ontogeny of vitellogenin-2. Twelve Kyoto Encyclopedia of Genes and Genomes pathways and two EcoToxModules were dysregulated in common in both species including the peroxisome proliferator-activated receptor (PPAR) signaling pathway and fatty acid metabolism. Similar to previously reported differences at the organismal level, DCCO were more responsive to EE2 exposure than JQ at the gene expression level. Our description of differences in transcriptional responses to EE2 in early life stage birds may contribute to a better understanding of the molecular basis for species differences. Environ Toxicol Chem 2024;43:772-783. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Developing a Novel Read-Across Concept for Ecotoxicological Risk Assessment of Phosphate Chemicals: A Case Study.

This study introduces a novel concept approach for a read-across assessment, considering species sensitivity differences among phosphate chemicals within structurally similar compound groups. Twenty-five organic chemicals, with a log Kow of 5 or less, were categorized into three functional groups based on acetylcholinesterase (AChE) inhibition as a specific mode of action (MOA). The short-term aquatic toxicity data (LC50) for fish, crustaceans, and insects were collected from the U.S. EPA Ecotoxicology (ECOTOX) Knowledgebase. A geometric mean calculation method was applied for multiple toxic endpoints. Performance metrics for the new read-across concept, including correlation coefficient, bias, precision, and accuracy, were calculated. Overall, a slightly higher overestimation (49.2%) than underestimation (48.4%) in toxicity predictions was observed in two case studies. In Case study I, a strong positive correlation (r = 0.93) between the predicted and known toxicity values of target chemicals was observed, while in Case study II, with limited information on species and their ecotoxicity, showed a moderate correlation (r = 0.75). Overall, the bias and precision for Case study I were 0.32 ± 0.01, while Case study II showed 0.65 ± 0.06; however, the relative bias (%) increased from 37.65% (Case study I) to 91.94% (Case study II). Bland-Altman plots highlight the mean differences of 1.33 (Case study I) and 1.24 (Case study II), respectively. The new read-across concept, focusing on AChE inhibition and structural similarity, demonstrated good reliability, applicability, and accuracy with minimal bias. Future studies are needed to evaluate various types of chemical substances, diverse modes of action, functional groups, toxic endpoints, and test species to ensure overall comprehensiveness and robustness in toxicity predictions.

Aflatoxin B1 exposure causes splenic pyroptosis by disturbing the gut microbiota-immune axis.

Aflatoxin B1 (AFB1) causes serious immunotoxicity and has attracted considerable attention owing to its high sensitivity and common chemical-viral interactions in living organisms. However, the sensitivity of different species to AFB1 widely varies, which cannot be explained by the different metabolism in species. The gut microbiota plays a crucial role in the immune system, but the interaction of the microbiota with AFB1-induced immunotoxicity still needs to be determined. Our results indicated that AFB1 exposure disrupted the structure of the gut microbiota and damaged the gut barrier, which caused translocation of microbiota metabolites, lipopolysaccharides, to the spleen. Subsequently, pyroptosis of the spleen was activated. Interestingly, AFB1 exposure had little effect on the splenic pyroptosis of pseudo-germfree mice (antibiotic mixtures eliminated their gut microbiota, ABX). Then, fecal microbiota transplant (FMT) and sterile fecal filtrate (SFF) were employed to validate the function of the gut microbiota and its metabolites in AFB1-induced splenic pyroptosis. The AFB1-disrupted microbiota and its metabolites significantly promoted splenic pyroptosis, which was worse than that in control mice. Overall, AFB1-induced splenic pyroptosis is associated with the gut microbiota and its metabolites, which was further demonstrated by FMT and SFF. The mechanism of AFB1-induced splenic pyroptosis was explored for the first time, which paves a new way for preventing and treating the immunotoxicity from mycotoxins by regulating the gut microbiota.

Zoledronic acid and ibandronate-induced nephrotoxicity in 2D and 3D proximal tubule cells derived from human and rat.

Drug-induced proximal tubule (PT) injury remains a serious safety concern throughout drug development. Traditional in vitro 2-dimensional (2D) and preclinical in vivo models often fail to predict drug-related injuries presented in clinical trials. Various 3-dimensional (3D) microphysiological systems (MPSs) have been developed to mimic physiologically relevant properties, enabling them to be more predictive toward nephrotoxicity. To explore the capabilities of an MPS across species, we compared cytotoxicity in hRPTEC/TERT1s and rat primary proximal tubular epithelial cells (rPPTECs) following exposure to zoledronic acid and ibandronate (62.5-500 µM), and antibiotic polymyxin B (PMB) (50 and 250 µM, respectively). For comparison, we investigated cytotoxicity using 2D cultured hRPTEC/TERT1s and rPPTECs following exposure to the same drugs, including overlapping concentrations, as their 3D counterparts. Regardless of the in vitro model, bisphosphonate-exposed rPPTECs exhibited cytotoxicity quicker than hRPTEC/TERT1s. PMB was less sensitive toward nephrotoxicity in rPPTECs than hRPTEC/TERT1s, demonstrating differences in species sensitivity within both 3D and 2D models. Generally, 2D cultured cells experienced faster drug-induced cytotoxicity compared to the MPSs, suggesting that MPSs can be advantageous for longer-term drug-exposure studies, if warranted. Furthermore, ibandronate-exposed hRPTEC/TERT1s and rPPTECs produced higher levels of inflammatory and kidney injury biomarkers compared to zoledronic acid, indicating that ibandronate induces acute kidney injury, but also a potential protective response since ibandronate is less toxic than zoledronic acid. Our study suggests that the MPS model can be used for preclinical screening of compounds prior to animal studies and human clinical trials.

Interspecies Differences in 6PPD-Quinone Toxicity Across Seven Fish Species: Metabolite Identification and Semiquantification.

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) is a recently identified contaminant that originates from the oxidation of the tire antidegradant 6PPD. 6PPD-Q is acutely toxic to select salmonids at environmentally relevant concentrations, while other fish species display tolerance to concentrations that surpass those measured in the environment. The reasons for these marked differences in sensitivity are presently unknown. The objective of this research was to explore potential toxicokinetic drivers of species sensitivity by characterizing biliary metabolites of 6PPD-Q in sensitive and tolerant fishes. For the first time, we identified an O-glucuronide metabolite of 6PPD-Q using high-resolution mass spectrometry. The semiquantified levels of this metabolite in tolerant species or life stages, including white sturgeon (Acipenser transmontanus), chinook salmon (Oncorhynchus tshawytscha), westslope cutthroat trout (Oncorhynchus clarkii lewisi), and nonfry life stages of Atlantic salmon (Salmo salar), were greater than those in sensitive species, including coho salmon (Oncorhynchus kisutch), brook trout (Salvelinus fontinalis), and rainbow trout (Oncorhynchus mykiss), suggesting that tolerant species might detoxify 6PPD-Q more effectively. Thus, we hypothesize that differences in species sensitivity are a result of differences in basal expression of biotransformation enzyme across various fish species. Moreover, the semiquantification of 6PPD-Q metabolites in bile extracted from wild-caught fish might be a useful biomarker of exposure to 6PPD-Q, thereby being valuable to environmental monitoring and risk assessment.

A systems approach reveals species differences in hepatic stress response capacity.

To minimize the occurrence of unexpected toxicities in early phase preclinical studies of new drugs, it is vital to understand fundamental similarities and differences between preclinical species and humans. Species differences in sensitivity to acetaminophen (APAP) liver injury have been related to differences in the fraction of the drug that is bioactivated to the reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI). We have used physiologically based pharmacokinetic modeling to identify oral doses of APAP (300 and 1000 mg/kg in mice and rats, respectively) yielding similar hepatic burdens of NAPQI to enable the comparison of temporal liver tissue responses under conditions of equivalent chemical insult. Despite pharmacokinetic and biochemical verification of the equivalent NAPQI insult, serum biomarker and tissue histopathology analyses revealed that mice still exhibited a greater degree of liver injury than rats. Transcriptomic and proteomic analyses highlighted the stronger activation of stress response pathways (including the Nrf2 oxidative stress response and autophagy) in the livers of rats, indicative of a more robust transcriptional adaptation to the equivalent insult. Components of these pathways were also found to be expressed at a higher basal level in the livers of rats compared with both mice and humans. Our findings exemplify a systems approach to understanding differential species sensitivity to hepatotoxicity. Multiomics analysis indicated that rats possess a greater basal and adaptive capacity for hepatic stress responses than mice and humans, with important implications for species selection and human translation in the safety testing of new drug candidates associated with reactive metabolite formation.

Physiological variables in machine learning QSARs allow for both cross-chemical and cross-species predictions

A major challenge in ecological risk assessment is estimating chemical-induced effects across taxa without species-specific testing. Where ecotoxicological data may be more challenging to gather, information on species physiology is more available for a broad range of taxa. Physiology is known to drive species sensitivity but understanding about the relative contribution of specific underlying processes is still elusive. Consequently, there remains a need to understand which physiological processes lead to differences in species sensitivity. The objective of our study was to utilize existing knowledge about organismal physiology to both understand and predict differences in species sensitivity. Machine learning models were trained to predict chemical- and species-specific endpoints as a function of both chemical fingerprints/descriptors and physiological properties represented by dynamic energy budget (DEB) parameters. We found that random forest models were able to predict chemical- and species-specific endpoints, and that DEB parameters were relatively important in the models, particularly for invertebrates. Our approach illuminates how physiological properties may drive species sensitivity, which will allow more realistic predictions of effects across species without the need for additional animal testing.

Vulvovaginal Candidiasis in Pregnancy-Between Sensitivity and Resistance to Antimycotics.

Vulvovaginitis with Candida spp. is the most common infection in women and the rate is increased during pregnancy. Antifungal prescription in pregnant women continues to present challenges and the decision must balance the risk of fetal toxicity with the benefits to the fetus and mother. Starting from the idea that clotrimazole is the most recommended antifungal in candidal vaginitis in pregnancy, we tested the sensitivity of different species of Candida spp. to other azoles, polyenes, and antimetabolites. This retrospective study (January to June 2019) assessed 663 pregnant women hospitalized for various pregnancy-related symptoms in which samples of phage secretion were taken. The laboratory results confirmed 21% of cases, indicating 140 positive mycologic samples. In this study, vaginal candidiasis was mostly related to the first trimester of pregnancy (53.57%,) and less related in the last trimester (17.14%). Candida albicans was the most frequent isolated strain in this study, accounting for 118 cases, followed by 16 strains of Candida glabrata and 6 cases of Candida krusei. The highest sensitivity for C. albicans was found in azoles, mostly in miconazole (93.2%), while C. krusei was completely resistant to polyene with low sensitivity in antimetabolites and even in some azoles, such as fluconazole. In our study, higher resistance rates to flucytosine were found, with C. glabrata and C. krusei exhibiting greater resistance than C. albicans.

A phenomics approach reveals interspecific differences in integrated developmental responses to chronic elevated temperatures.

Phenomics, high-dimensional organismal phenotyping, is advanced as a solution to quantifying complex developmental responses to elevated temperatures. 'Energy proxy traits' (EPTs) measure the phenotype as a spectrum of energy values across different temporal frequencies from pixel value fluctuations of video. Although they have proven effective in measuring the biology of complex and dynamic developing organisms, their utility in assessing environmental sensitivity of different species is untested. Using EPTs, we assess the relative thermal sensitivities of embryos of three species of freshwater snail with marked differences in their developmental event timings. Embryos of Lymnaea stagnalis, Radix balthica and Physella acuta were videoed hourly for the duration of their embryonic development at two temperatures: 20°C and 25°C. The video was used to calculate EPTs for the duration of their embryonic development, and during discrete physiological windows in development. Changes in energy spectra during development identified marked differences in thermal sensitivities between species, and suggest a relatively heightened sensitivity of gross rates of embryonic physiology and behaviour in embryos of R. balthica, developmental-window-specific thermal responses that reflect ontogenetic differences in observable physiologies, and temperature-induced changes in physiological event timing. EPTs enabled comparison of high-dimensional spectral phenotypes, providing a unique capability for assessing sensitivity continuously in developing individuals. Such integrative and scalable phenotyping is a prerequisite for improved understanding of the sensitivity of early life stages of different species.

Intestinal organoids as an in vitro platform to characterize disposition, metabolism, and safety profile of small molecules

Intestinal organoids derived from LGR5+ adult stem cells allow for long-term culturing, more closely resemble human physiology than traditional intestinal models, like Caco-2, and have been established for several species.Here we evaluated intestinal organoids for drug disposition, metabolism, and safety applications. Enterocyte-enriched human duodenal organoids were cultured as monolayers to enable bidirectional transport studies. 3D enterocyte-enriched human duodenal and colonic organoids were incubated with probe substrates of major intestinal drug metabolizing enzymes (DMEs). To distinguish human intestinal toxic (high incidence of diarrhea in clinical trials and/or black box warning related to intestinal side effects) from non-intestinal toxic compounds, ATP-based cell viability was used as a readout, and compounds were ranked based on their IC50 values in relation to their 30-times maximal total plasma concentration (Cmax). To assess if rat and dog organoids reproduced the respective in vivo intestinal safety profiles, ATP-based viability was assessed in rat and dog organoids and compared to in vivo intestinal findings when available.Human duodenal monolayers discriminated high and low permeable compounds and demonstrated functional activity for the main efflux transporters Multi drug resistant protein 1 (MDR1, P-glycoprotein P-gp) and Breast cancer resistant protein (BCRP). Human 3D duodenal and colonic organoids also showed metabolic activity for the main intestinal phase I and II DMEs. Organoids derived from specific intestinal segments showed activity differences in line with reported DMEs expression. Undifferentiated human organoids accurately distinguished all but one compound from the test set of non-toxic and toxic drugs. Cytotoxicity in rat and dog organoids correlated with preclinical toxicity findings and observed species sensitivity differences between human, rat, and dog organoids.In conclusion, the data suggest intestinal organoids are suitable in vitro tools for drug disposition, metabolism, and intestinal toxicity endpoints. The possibility to use organoids from different species, and intestinal segment holds great potential for cross-species and regional comparisons.

Misadventures in Toxicology: Concentration Matters for Testosterone-Induced Neurotoxicity.

Testosterone is the predominant androgen in men and has important physiological functions. Due to declining testosterone levels from a variety of causes, testosterone replacement therapy (TRT) is increasingly utilized, while testosterone is also abused for aesthetic and performance-enhancing purposes. It has been increasingly speculated that aside from more well-established side effects, testosterone may cause neurological damage. However, the in vitro data utilized to support such claims is limited due to the high concentrations used, lack of consideration of tissue distribution, and species differences in sensitivity to testosterone. In most cases, the concentrations studied in vitro are unlikely to be reached in the human brain. Observational data in humans concerning the potential for deleterious changes in brain structure and function are limited by their inherent design as well as significant potential confounders. More research is needed as the currently available data are limited; however, what is available provides rather weak evidence to suggest that testosterone use or abuse has neurotoxic potential in humans.

An ecotoxicological approach can complement the assessment of natural waters from Portuguese reservoirs?

Within the scope of the European Water Framework Directive (WFD), the scientific community recognized clear opportunities to take advantage of the use of ecotoxicological tools in water quality assessments. In this perspective, bioassays and biomarkers were suggested to contribute to the integration of the chemical and biological conditions, and thus to provide an overall insight into the quality of a water body. This study aimed to assess whether current bioassays as feeding rate assays with Daphnia longispina and growth inhibition assays with Lemna minor are suitable to detect potential ecotoxicity, using waters from Portuguese reservoirs. Several sampling sites were defined in reservoirs (Miranda, Pocinho, and Alqueva). The samplings were conducted in autumn of 2018 and spring of 2019. Total chlorophyll, lipid peroxidation, and proline content were also evaluated in L. minor. Results demonstrated that D. longispina showed some sensitivity to water treatments; however, the results were difficult to interpret since no reason or trend can be accurate. All parameters of L. minor did not show sensitivity to detect potential ecotoxicological risks associated with natural water understudy, since no discrimination among the water treatments was recorded. However, biomarkers/bioassays proved to be concordant to each other. Under the conditions evaluated here (reservoirs and sampling periods), the biological responses observed were not consistent, clear, and coherent with the physical-chemical parameters and chemical analyses performed, suggesting that the ecotoxicological tools selected were not sensitive to assess water quality in this type of ecosystems. In this sense, species of different trophic levels are recommended for ecotoxicological analyses due to differences in species sensitivities.

Derivation of water quality criteria for glyphosate and its formulations to protect aquatic life in China.

Extensive use of the herbicide glyphosate leads to a high detection rate in the environment and potential risks to nontarget aquatic life. China ranks first globally in the production and consumption of glyphosate, but there are no glyphosate water quality criteria (WQCs) for protecting aquatic life. Here, data on the acute and chronic toxicity of glyphosate and glyphosate-based formulations (GBFs) to freshwater aquatic life were collected and screened. Significant differences in species sensitivity distributions (SSDs) and toxicity values for acute or chronic toxicity were found between glyphosate and GBFs. The hazardous concentrations for 5% of species (HC5) of glyphosate or GBFs between native and nonnative species were different, and native species were found to be more sensitive to the toxicity of glyphosate. The acute and chronic WQCs derived with the SSD method for glyphosate based on the toxicity data for native species in China were 3.35 and 0.26mg/L, respectively, and those found for GBFs were 0.21 and 0.005mg/L, respectively. The WQCs in this study were quite different from those estimated using similar statistical extrapolation methods in other countries, which reflects the differences in species sensitivity to glyphosate toxicity in different regions. The hazard quotients (HQs) were calculated based on the WQCs and concentrations of glyphosate in some surface waters in China and indicated that glyphosate exhibits medium or high hazard risk in some samples of Tai Lake, surface water in Guiyang, fishpond water in Chongqing, rural drinking water, and surface water and reservoir water in Henan Province. The WQCs of glyphosate and GBFs have scientific significance for the exposure and pollution control of herbicide formulations and the protection of aquatic life in China.

Characterization of marine-derived halogenated indoles as ligands of the aryl hydrocarbon receptor

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor thought to mediate a number of physiological roles in the body, is becoming a target of interest for the development of new therapeutics. However, previous research has demonstrated that the downstream effects of AhR ligands cannot be predicted based simply on whether a ligand acts as an agonist or antagonist and the persistence of AhR signaling is thought to be a key determining feature. The current study investigated the AhR activity of four halogenated indoles isolated from the New Zealand red alga, Rhodophyllis membranacea: 4,7-dibromo-2,3-dichloroindole (4DBDCI), 7-bromo-2,3-dichloro-6-iodoindole (BDCII), 6,7-dibromo-2,3-dichloroindole (6DBDCI) and 2,6,7-tribromo-3-chloroindole (TBCI). Their ability to activate AhR signaling, measured as CYP1A1 activity via the ethoxyresorufin O-deethylase (EROD) assay, was determined in human HepG2, mouse Hepa1c1c7 and rat H4IIE liver cancer cells. All four compounds induced CYP1A1 activity in HepG2 cells, suggesting they all acted as AhR agonizts. 4DBDCI was particularly efficacious, inducing an 11-fold increase. Hepa1c1c7 and H4IIE cells, however, were generally less responsive to the halogenated indoles. All four compounds were persistent AhR agonizts, inducing peak CYP1A1 activity after 72 h. Moreover, the 2,3,6,7-substituted BDCII, 6DBDCI and TBCI, but not 4DBDCI, competed with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for AhR binding as observed by the inhibition of TCDD-induced CYP1A1 activity. Overall, the current study has characterized four previously untested AhR ligands, highlighting differences in species sensitivity and persistence of signaling to provide a framework for their potential future use.

Dead or Alive: Drivers of Wind Mortality Initiate Multiple Disturbance Regime in a Temperate Primeval Mountain Forest

The driving forces of tree mortality following wind disturbances of mountain mixed European temperate forests belongs among issues not comprehensively resolved. Hence, we aimed to elucidate the key factors of tree resistance to historical severe disturbance events in the Boubínský Primeval Forest, one of the oldest forest reserves in the Czech Republic. By using spatially explicit tree census, dendrochronological and soil data, we study spatial and temporal patterns of past disturbances and mathematically compared selected characteristics of neighboring trees that were killed by a severe storm in 2017 and those that remained undisturbed. The tendency of trees toward falling was primarily driven edaphically, limiting severe events non-randomly to previously disturbed sites occupied by hydromorphic soils and promoting the existence of two spatially-separated disturbance regimes. While disturbed trees usually recruited in gaps and experienced only one severe release event, surviving trees characteristically regenerated under the canopy and were repeatedly released. Despite the fact that disturbed trees tended to reach both lower ages and dimensions than survivors, they experienced significantly higher growth rates. Our study indicates that slow growth with several suppression periods emerged as the most effective tree strategy for withstanding severe windstorms, dying of senescence in overaged life stage. Despite the selective impact of the Herwart storm on conifer population, we did not find any difference in species sensitivity for most characteristics studied. We conclude that the presence of such ancient, high-density wood trees contributes significantly to the resistance of an entire stand to severe storms.

Using Transcriptomics and Metabolomics to Understand Species Differences in Sensitivity to Chlorpyrifos in Japanese Quail and Double-Crested Cormorant Embryos.

Modern 21st-century toxicity testing makes use of omics technologies to address critical questions in toxicology and chemical management. Of interest are questions relating to chemical mechanisms of toxicity, differences in species sensitivity, and translation of molecular effects to observable apical endpoints. Our study addressed these questions by comparing apical outcomes and multiple omics responses in early-life stage exposure studies with Japanese quail (Coturnix japonica) and double-crested cormorant (Phalacrocorax auritus), representing a model and ecological species, respectively. Specifically, we investigated the dose-dependent response of apical outcomes as well as transcriptomics and metabolomics in the liver of each species exposed to chlorpyrifos, a widely used organophosphate pesticide. Our results revealed a clear pattern of dose-dependent disruption of gene expression and metabolic profiles in Japanese quail but not double-crested cormorant at similar chlorpyrifos exposure concentrations. The difference in sensitivity between species was likely due to higher metabolic transformation of chlorpyrifos in Japanese quail compared to double-crested cormorant. The most impacted biological pathways after chlorpyrifos exposure in Japanese quail included hepatic metabolism, oxidative stress, endocrine disruption (steroid and nonsteroid hormones), and metabolic disease (lipid and fatty acid metabolism). Importantly, we show consistent responses across biological scales, suggesting that significant disruption at the level of gene expression and metabolite profiles leads to observable apical responses at the organism level. Our study demonstrates the utility of evaluating effects at multiple biological levels of organization to understand how modern toxicity testing relates to outcomes of regulatory relevance, while also highlighting important, yet poorly understood, species differences in sensitivity to chemical exposure. Environ Toxicol Chem 2021;40:3019-3033. © 2021 SETAC.

Relative sensitivity of duckweed Lemna minor and six algae to seven herbicides.

We investigated the relative sensitivity of duckweed Lemna minor and six species of algae to seven herbicides, using an efficient high-throughput microplate-based toxicity assay. First, we assessed the sensitivity of L. minor to the seven herbicides, and then we compared its sensitivity to that of previously published data for six algal species based on EC50 values. For five herbicides, the most sensitive species differed: L. minor was most sensitive to cyclosulfamuron: Raphidocelis subcapitata was most sensitive to pretilachlor and esprocarb: Desmodesmus subspicatus was most sensitive to pyraclonil; and Navicula pelliculosa was most sensitive to pyrazoxyfen. Simetryn was evenly toxic to all species, whereas 2,4-D was evenly less toxic, with only small differences in species sensitivity. These results suggested that a single algal species cannot represent the sensitivity of the primary producer assemblage to a given herbicide. Therefore, to assess the ecological effects of herbicides, aquatic plant and multispecies algal toxicity data sets are essential.