{"topic_id":"evidence_exotic_amphibian_toxicology","category":"evidence","context":"---\ntopic_id: evidence_exotic_amphibian_toxicology\ncategory: evidence\ntitle: \"Evidence cluster — Pet amphibian (anuran) toxicology (peer-reviewed, Europe PMC)\"\nlang: en\nsource: \"Europe PMC (Europe PubMed Central) REST search, first-hand peer-reviewed abstracts, pulled 2026-08-01\"\nsource_file: pdf-raw/evidence/europepmc_amphibian_toxicology_2026-08-01.txt\ndate_parsed: 2026-08-01\ntokens_estimated: 5482\nverification:\n  method: substring_match\n  claims: 12\n  passed: 12\n  date: 2026-08-01\nsource_document: \"Peer-reviewed Pet amphibian toxicology literature (Europe PMC, first-hand abstracts)\"\ncitation:\n  authority: \"Europe PMC\"\n  title: \"Evidence cluster — Pet amphibian (anuran) toxicology (peer-reviewed, Europe PMC)\"\n  url: \"https://www.ebi.ac.uk/europepmc/\"\n  retrieved: \"2026-08-01\"\n  doc_type: \"first-hand abstracts (Europe PMC REST)\"\n  needs_review: false\n---\n\n# Evidence: Pet amphibian (anuran) toxicology\n\nSource: Europe PMC (Europe PubMed Central) REST search — first-hand peer-reviewed abstract records, pulled 2026-08-01.\nQueries covered toxicology, poisoning, intoxication, heavy metals, mycotoxins and (for relevant taxa) envenomation for anuran.\nThe cluster returns **12** representative studies with abstracts below. Abstract text is verbatim from source; each study is traceable by PMID.\n\n## Studies\n- **PMID 41483836 (2026, Toxicology letters)** — Predicting acute developmental toxicity of chemicals in embryos of the African clawed frog (Xenopus laevis): Calibration and validation of regression-based quantitative structure activity relationship models for hazard assessment of chemicals in anuran amphibians.. Abstract (opening): Global decline of amphibian populations has been correlated with a range of endogenous and exogenous variables including their unique physiology and ecology, exposure to chemicals, habitat reduction, climate change, as well as biological hazards such as emerging infectious diseases. The African clawed frog (Xenopus laevis) is an OECD test species used in toxicity testing as a specific proxy for humans and environmentally relevant species, for which acute toxicity data for a range of chemicals have been generated historically by industry, a number of public health agencies and academia. Of particular relevance are mechanistic effects of endocrine-active substances on metamorphosis and the thyroid axis, resulting in developmental toxicity. From such toxicity data, no open-source quantitative structure-activity relationships (QSARs) have been developed as in silico tools to predict such toxicity for data-poor chemicals in X. laevis. Such QSAR models can provide a quantitative starting point for the hazard assessment of chemicals in other anuran amphibians. This manuscript provides a description of the data collection and curation from the largest historical databases including the US EPA ECOTOX knowledgebase and the Ortiz-Santaliestra databases available for Xenopus embryos as acute median lethal concentrations (LC<sub>50</sub>-12 h) for a total of 349 unique structures and 1978 individual entries. After data curation, the database contained 359 individual entries for a total of 175 compounds, and were computed using the negative logarithm of molar concentrations expressed as 12 h log 1/LC50 mmol/L. Subsequently, the database was then split into training set, test set and prediction set with 120, 40 and 13 compounds, respectively. These datasets were then used for the development and validation of two different QSAR models: 1. A k-Nearest Neighbours (k-NN) models using istKNN (in silico tools - KNN). 2. A multiple linear regression model (MLR) using the QSARINS (QSAR-INSUBRIA) software version 2.2.4. Overall, the QSAR models performed well for predicting acute toxicity of chemicals in Xenopus embryos and the MLR model performed slightly better than the k-NN model with correlation coefficients of 0.76 and 0.75 and root mean square errors of 0.63 and 0.67, respectively. However, underestimation of predictions for highly toxic compounds were observed and these limitations are discussed for both the k-NN and multiple linear regression model in the light of mechanistic interpretation and expert knowledge. Variability in the experimental datasets as well as under-representation of the most toxic compounds in the database are highlighted as major drivers influencing such underpredictions. Future directions from the present work include the modelling of other endpoints and developmental stages as well as other amphibian species using the available, although limited, data. Overall, it can be foreseen in the near future that such databases and models will be important to develop more performant in silico models, and ultimately to develop NAMs for ecotoxicity assessment of chemicals in anuran amphibians while reducing animal testing.\n  Source: https://pubmed.ncbi.nlm.nih.gov/41483836/\n- **PMID 41670719 (2026, Archives of environmental contamination and toxicology)** — Determining the Impacts of an Aquatic Copper Exposure to Ambystoma Gracile (Northwestern Salamander).. Abstract (opening): This study investigated the acute and subchronic toxicity of copper on Northwestern Salamander (Ambystoma gracile) larvae under varying water hardness conditions. Acute exposure experiments demonstrated that larvae in soft water had lower LC50 values than those in moderately hard water, with LC50 values of 33.16 µg/L and 1383 µg/L, respectively. Subchronic exposure to copper resulted in delayed development, reduced survival, and growth inhibition, with a 35-day LC50 of 28.97 µg/L. Gene expression analysis was conducted for the acute copper exposures and revealed a significant increase in metallothionein 1 (mt1), a protein indicative of metal detoxification response in most vertebrates. However, expression levels of thyroid hormone receptor genes (thra, thrb) were unchanged. Additionally, there was no impact on the expression of an estrogen receptor (esr1α) and a deiodinase (dio1) gene. Comparisons with previous studies on anuran species highlighted both similarities and differences in copper sensitivity and developmental responses depending on the anuran species. This variation underscores the importance of species-specific studies in understanding the broader ecological impact of copper pollution on amphibians. Finally, this research provides critical data on a representative caudate amphibian species, a taxa that is typically not included in ecological risk assessments due to lack of toxicity data.\n  Source: https://pubmed.ncbi.nlm.nih.gov/41670719/\n- **PMID 41793491 (2026, Bulletin of environmental contamination and toxicology)** — Subchronic Exposure to Nonylphenol Ethoxylate at Environmentally Relevant Level Promotes Mutagenic, Neurotoxic, and Pro-oxidant Effects in Bullfrog Tadpoles.. Abstract (opening): Nonylphenol compounds released into aquatic environments have been shown to exert deleterious effects on aquatic organisms. Amphibians, particularly during larval stages, are highly vulnerable to chemical stressors and are chronically exposed to pollutants such as nonylphenol ethoxylate (NPE). This study evaluated the sublethal effects of environmentally relevant concentrations of NPE (30 µg L−1) under sub-chronic exposure in Aquarana catesbeiana tadpoles (Gosner stage 25), with emphasis on mutagenic, neurotoxic, and oxidative responses. The analyses included blood cell composition, frequency of micronuclei (MN) and erythrocytic nuclear abnormalities (ENAs), acetylcholinesterase (AChE) activity in brain and muscle tissues, and oxidative stress biomarkers (lipid peroxidation and protein carbonylation) in blood. Results demonstrated that NPE exposure induced clastogenic and aneugenic effects in erythrocytes, impaired central and muscular cholinergic function, and triggered oxidative stress in blood. These findings highlight the NPE potential to disrupt critical physiological systems in amphibians.\n  Source: https://pubmed.ncbi.nlm.nih.gov/41793491/\n- **PMID 42146017 (2026, Frontiers in physiology)** — Physiological responses and adaptive mechanisms of amphibians and reptiles to multiple interacting environmental stressors: an integrative review.. Abstract (opening): This integrative review synthesizes current knowledge on the physiological responses and adaptive mechanisms of amphibians and reptiles to multiple interacting environmental stressors, with particular emphasis on synergistic effects among temperature, hydric stress, disease, and pollution. Given the stronger empirical basis for amphibians in the existing literature, amphibian responses are covered in greater depth, while reptile-specific physiology, immunology, and emerging infectious diseases are explicitly addressed in dedicated sections throughout the review. Critical thermal tolerance analyses reveal that approximately 7.5% of amphibian species will exceed their physiological limits under a 4 °C warming scenario, with tropical lowland species already operating near their CTmax thresholds. Thermal plasticity is limited, with acclimation responses averaging only 0.13 °C increase in CTmax per 1 °C environmental warming-insufficient to track rapid climate change. Water balance regulation shows dramatic interspecific variation, with cutaneous resistance ranging from 0.05 s/cm in aquatic amphibians to >1000 s/cm in desert-adapted reptiles. Synergistic interactions between thermal and hydric stress significantly amplify vulnerability, particularly in dehydration scenarios that reduce critical thermal limits. Chemical pollutants, including heavy metals and pesticides, cause developmental abnormalities (535% increase in malformation frequency), immunosuppression, and endocrine disruption across multiple life stages. Emerging infectious diseases, particularly chytridiomycosis (<i>Batrachochytrium dendrobatidis</i> and <i>B. salamandrivorans</i>) and ranaviruses, drive mass mortality events globally, with co-infections exacerbating population declines. Climate change intensifies disease susceptibility through stress-mediated immunosuppression and altered pathogen dynamics. Adaptive capacity varies markedly among species. While amphibians exhibit strong phenological responses (2-4× greater than other taxa), genetic adaptation potential remains limited by narrow dispersal abilities and habitat fragmentation. Microhabitat buffering can reduce thermal extremes by several degrees but depends critically on habitat structural integrity. This review demonstrates that the pace of anthropogenic change challenges the adaptive capacity of most species, necessitating integrated conservation strategies including microhabitat preservation, climate corridor establishment, pollution mitigation, disease surveillance, and <i>ex-situ</i> conservation programs.\n  Source: https://pubmed.ncbi.nlm.nih.gov/42146017/\n- **PMID 40298996 (2025, Bulletin of environmental contamination and toxicology)** — Lambda-Cyhalothrin Effect on the Swimming Behavior of Boana pulchella (Anura: Hylidae) Tadpoles.. Abstract (opening): Boana pulchella is an anuran species widely distributed in Neotropical South America and commonly abundant in the Argentine Pampas. The aim of this study was to evaluate the effects of the commonly used insecticide lambda-cyhalothrin on the swimming performance of B. pulchella tadpoles exposed to environmentally relevant concentration in a laboratory bioassay. Mean velocity was measured in two treatments of 1.5 and 10 µg/L and a control, after 2-h and 96-h exposures. The mean speed displacement was estimated using the video analysis software Tracker<sup>®</sup>. No mortality was detected. However, tail flexion was observed in all tadpoles in both treatments throughout the entire exposure period, which was not observed in the controls. Swimming velocity was significantly lower in the exposed treatments compared to the control, and lower at the higher concentration exposure. It is concluded that exposure to field-relevant lambda-cyhalothrin concentrations affects the morphology and swimming behavior of B. pulchella, thus influencing its competitive fitness and potentially affecting non-target amphibian assemblages.\n  Source: https://pubmed.ncbi.nlm.nih.gov/40298996/\n- **PMID 41008613 (2025, Biomolecules)** — Gene Duplication, Translocation, and Molecular Evolution of &lt;i&gt;Dmrt1&lt;/i&gt; and Related Sex-Determining Genes in Anurans.. Abstract (opening): Sex determination, the developmental process that directs embryos toward male or female fates, is controlled by master sex-determining genes whose origins and evolutionary dynamics remain poorly understood outside of a few model systems. In contrast to the highly differentiated sex chromosomes of mammals, birds, and <i>Drosophila</i>, most anurans (frogs and toads) maintain homomorphic sex chromosomes that exhibit a rapid turnover, even among closely related species. Master sex-determining genes evolve via gene duplication or via allelic diversification, and sex chromosome turnover is driven by gene translocation or novel mutations in the existing genes involved in the sexual developmental pathway. To uncover the mechanisms underlying the emergence of master sex-determining genes and sex chromosome turnover, we analyzed 53 published anuran genomes and one caecilian genome (>200 Mya divergence) and available transcriptomes. We asked how often master sex-determining genes arise by gene duplication, whether and how often gene translocation associates with sex chromosome turnover, and if master sex-determining genes evolve under positive selection. We find that chromosome-level synteny is remarkably conserved, with only a few fusions or fissions and no evidence for translocation of four candidate master sex-determining genes (<i>Dmrt1</i>, <i>Foxl2</i>, <i>Bod1l</i>, and <i>Sox3</i>). Only <i>Dmrt1</i> duplicated in 3 out of 50 species (excluding tetraploid <i>Xenopus</i>), and it showed strong testis-biased expression in all 8 species with available gonadal expression data. While <i>Dmrt1</i> has evolved under purifying selection, <i>Dmrt1</i> duplicates exhibit elevated nonsynonymous substitution rates and tendency towards positive selection. Lineage-specific amino acid changes were observed in the conserved DM domain of <i>Dmrt1</i>. These results demonstrate that, in anurans, master sex-determining genes rarely arise via gene duplication, and more likely evolve via allelic diversification. Sex chromosome turnover is not associated with gene translocation and is more likely driven by mutations on genes involved in sexual developmental pathways. All candidate sex-determining genes were under strong purifying selection, with the exception of duplications which are linked to positive selection. Our results suggest future research on anuran sex determination and sex chromosome evolution should focus on identifying allelic diversification and novel mutations on genes involved in sexual developmental pathways.\n  Source: https://pubmed.ncbi.nlm.nih.gov/41008613/\n- **PMID 40181708 (2025, Journal of morphology)** — Perichordal Vertebral Column Formation in Rana kobai.. Abstract (opening): The vertebral column of anurans exhibits morphological diversity that is often used in phylogenetic studies. The family Ranidae is one of the ecologically most successful groups of anurans, with the genus Rana being distributed broadly in Eurasia. However, there are relatively sparse detailed studies on the development of the vertebral column in Rana species, and images of the entire axial skeleton have seldom been illustrated till date. Here, we provide an illustrated description on the development of the entire vertebral column in Rana kobai, a Japanese small frog from the Amami Islands. Our observation of double-stained skeletal specimens revealed that in R. kobai, the original atlas and the first dorsal are fused into one vertebra, and the ninth neural arch is fused with the tenth arch in half of the examined larvae. Anuran vertebral column development is classified into two modes, perichordal and epichordal. Rana species undergo the typical perichordal mode of centrum formation. Kemp and Hoyt (1969) described that centrum formation in R. pipiens starts from a saddle-shaped bone on the dorsal half of the notochord. Nevertheless, our detailed observations revealed that centrum ossification initially emerges at the base of the paired neural arches and then forms the saddle-shaped bone. In Xenopus, a species with epichordal centra, centrum formation starts from a pair of ovoid bone elements at the base of the neural arches. Overall, our results imply that centrum ossification starts from the base of neural arches in anurans, irrespective of whether it is perichordal or epichordal. Our observations also revealed the presence of the crescent-shaped cartilage domain in the intervertebral region in R. kobai. The location of the crescent-shaped domain in R. kobai is consistent with that of the intercentrum in Ichthyostega and several temnospondyls. Based on our observations, we propose a hypothesis on the difference between perichordal and epichordal modes in light of evolution.\n  Source: https://pubmed.ncbi.nlm.nih.gov/40181708/\n- **PMID 41561475 (2025, Frontiers in toxicology)** — Comparative assessment of solvents toxicity using early life stages of amphibians and cell lines: a case study with dimethyl sulfoxide.. Abstract (opening): The reduction in the number of animals being used in experimental assays has been a concern of the scientific community. In this sense, non-animal alternative methods have been increasingly tested. This study intended to explore how cell-based responses compare to organismal outcomes and if the former models could contribute to minimizing the number of live animals needed in subsequent stages of hazard/risk assessment of chemicals on amphibians. For this, the toxicity of the commonly used solvent dimethyl sulfoxide (DMSO) was assessed in early life stages (embryos and tadpoles) of two anuran species (<i>Xenopus laevis</i> and <i>Pelophylax perezi</i>) and in 2 cell lines of <i>X. laevis</i> (A6 and XTC-2). In the <i>in vivo</i> assays, mortality, teratogenic effects, and biometric parameters were evaluated, while for <i>in vitro</i> assays, the assessed endpoint was viability. Overall, the obtained data suggest similar sensitivity of both species and life stages to DMSO. The 96 h-LC<sub>50</sub> estimated for embryos and tadpoles were, respectively, 2.19% and 2.56% for <i>X. laevis</i> and 3.19 and 3.41 for <i>P. perezi</i>. The solvent DMSO induced several malformations in early life stages, which may have implications for the fitness of organisms at later stages. A slightly higher sensitivity to DMSO was observed in the <i>in vivo</i> approaches comparatively to <i>in vitro</i> approach (72 h-LC<sub>50</sub> of 3.10% and 2.62% for A6 and XTC-2, respectively), though it can not be considered significantly different. As such, it is suggested that the latter approach may be considered to serve for first screenings of the ecotoxicity of organic solvents. Such a strategy of using <i>in vitro</i> assays as screening tools, has the potential to reduce the number of animals to be used in subsequent <i>in vivo</i> testing phases by providing information for the refinement of concentrations to be tested in <i>in vivo</i> assays, thereby supporting both reduction and replacement objectives.\n  Source: https://pubmed.ncbi.nlm.nih.gov/41561475/\n- **PMID 39855321 (2025, Environmental toxicology and pharmacology)** — Impact of environmentally relevant concentrations of glyphosate on Boana faber tadpoles exposed in the laboratory: Morphological and functional markers.. Abstract (opening): This study evaluated the effects of a glyphosate-based herbicide on the oxidative balance, energy metabolism, and body condition indices in tadpoles of Boana faber. Anuran spawns were collected, and after hatching and reaching Gosner stage 25, they were acclimated and exposed (168 hours) to concentrations of glyphosate (G1: 65, G2: 260, and G3: 520 µg/L). The body condition markers revealed a significant decrease in all these biomarkers in G2 and G3. Tadpoles exposed to the highest concentration of glyphosate showed an increase in superoxide dismutase activity and the maintenance of lipoperoxidation levels. Carbonyl proteins of animals of G1 and G2 groups showed a reduction that coincides with increased catalase activity. Glycogen decreased in all exposed groups, indicating that this polysaccharide was used for energy production. The body condition markers established here are a non-invasive and promising way of assessing the health status of animals.\n  Source: https://pubmed.ncbi.nlm.nih.gov/39855321/\n- **PMID 41295741 (2025, Veterinary sciences)** — Hematology Reference Values for the Iberian Ribbed Newt (&lt;i&gt;Pleurodeles waltl&lt;/i&gt;) Under Human Care.. Abstract (opening): The Iberian ribbed newt (<i>Pleurodeles waltl</i>) is a salamander in the Salamandridae family. Endemic to the Iberian Peninsula and North Africa, it is not commonly found in zoological institutions or wildlife rescue centers. As in other species, routine blood analysis of amphibians under human care is highly recommended, forming an essential component of preventive medicine and effective clinical management. However, despite the great utility of hematological parameters for the diagnosis and prevention of diseases in amphibians, the lack of reliable reference values for many species severely limits their clinical use. The aim of this study is to establish preliminary reference values (RV) for the main hematological parameters in the Iberian ribbed newt. Blood samples were taken from healthy adult individuals (<i>n =</i> 30), females (<i>n =</i> 9) and males (<i>n</i> = 21) maintained under controlled conditions in two zoological institutions. A complete hematological analysis was conducted, which included measurements of hematocrit, total erythrocyte and leukocyte counts, as well as a leukocyte differential. The reference intervals were established according to the guidelines provided by the American Society for Veterinary Clinical Pathology (ASVCP) for sample sizes between 20 and 40 individuals. No significant sex-related differences were detected in the hematological parameters analyzed. Despite the broad reference ranges obtained, these preliminary data provide an essential foundation for the clinical assessment and preventive medical management of <i>P. waltl</i> under human care. Expanding the dataset through collaboration with additional institutions will further refine and improve the accuracy and clinical utility of these reference values.\n  Source: https://pubmed.ncbi.nlm.nih.gov/41295741/\n- **PMID 41234787 (2025, Royal Society open science)** — Arid habitats intensify sexual conflict in invasive cane toads (&lt;i&gt;Rhinella marina&lt;/i&gt;).. Abstract (opening): Amplexus by male cane toads (<i>Rhinella marina</i>) impairs a female's mobility and may impose a risk of drowning. Near the arid-zone edge of the toads' Australian invasion, artificial ponds provide the only permanent open water. Cane toads must access water to hydrate every few nights, creating a potential for sexual conflict. Our field-based experiments show that a female toad that approaches one of these steep-sided dams encounters numerous reproductively active males, most of which are facing the shore. When amplexed by these males, she may find herself in deep water even close to the shore and is vulnerable to drowning. In trials with tethered females, toads amplexed in deep water could not hold their heads above the water's surface. Demographic effects of this sexual conflict are evident from population surveys: toad populations around dams are strongly male-biased whereas females are concentrated at mesic refuges around buildings that provide less dangerous conditions. Even around the same dam, female toads are often found on land whereas most males are found in the water. If sexual conflict around scarce waterbodies is lethal for female toads, we might reduce recruitment by allowing dense populations of male toads to persist.\n  Source: https://pubmed.ncbi.nlm.nih.gov/41234787/\n- **PMID 40274765 (2025, Nature communications)** — Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins.. Abstract (opening): Dinoflagellates and cyanobacteria produce saxitoxin (STX) and ~50 congeners that disrupt bioelectrical signals by blocking voltage-gated sodium channels (Na<sub>V</sub>s). Consuming seafood carrying these toxins causes paralytic shellfish poisoning (PSP). Although Na<sub>V</sub>s and anuran STX binding proteins (saxiphilins, Sxphs) use convergent STX binding modes, the structural basis for STX congener recognition is unknown. Here, we show that American bullfrog (Rana catesbeiana) RcSxph and High Himalaya frog (Nanorana parkeri) NpSxph sequester STX congeners using a 'lock and key' mode shared with STX. Importantly, functional studies demonstrate that Sxph 'toxin sponges' reverse Na<sub>V</sub> block by multiple STX congeners and detect these toxins in a radioligand binding assay (RBA) used for environmental testing. Together, our study establishes how Sxphs sequester select neurotoxins and uncover STX congener-specific interactions distinct from Na<sub>V</sub>s. These findings expand understanding of toxin sponge action and provide a foundation for strategies to monitor and mitigate the harmful effects of STX congeners.\n  Source: https://pubmed.ncbi.nlm.nih.gov/40274765/\n\nSource text: `pdf-raw/evidence/europepmc_amphibian_toxicology_2026-08-01.txt` (Europe PMC first-hand abstracts, pulled 2026-08-01).\n","sources":["Europe PMC — Evidence cluster — Pet amphibian (anuran) toxicology (peer-reviewed, Europe PMC) (retrieved 2026-08-01)"],"source":{"authority":"Europe PMC","title":"Evidence cluster — Pet amphibian (anuran) toxicology (peer-reviewed, Europe PMC)","url":"https://pubmed.ncbi.nlm.nih.gov/41483836/","retrieved":"2026-08-01","ref":"PMID 41483836","doc_type":"official PDF","source_document":"Peer-reviewed Pet amphibian toxicology literature (Europe PMC, first-hand abstracts)","verification_file":"pdf-raw/evidence/europepmc_amphibian_toxicology_2026-08-01.txt"},"source_document":"Peer-reviewed Pet amphibian toxicology literature (Europe PMC, first-hand abstracts)","source_file":"pdf-raw/evidence/europepmc_amphibian_toxicology_2026-08-01.txt","tokens_estimated":600,"generated_at":null,"tip":"Use /api/v1/topics to discover more topics. /api/v1/nutrient for precise single-point queries. /api/v1/cross_compare for 2-3 standard comparisons."}