Current Research in Toxicology最新文献

{"title":"An in vitro toxicological assessment of two electronic cigarettes: E-liquid to aerosolisation","authors":"E. Bishop,&nbsp;F. Miazzi,&nbsp;S. Bozhilova,&nbsp;N. East,&nbsp;R. Evans,&nbsp;D. Smart,&nbsp;M. Gaca,&nbsp;D. Breheny,&nbsp;D. Thorne","doi":"10.1016/j.crtox.2024.100150","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100150","url":null,"abstract":"<div><p>Interest in the toxicological assessment of iterations of e-cigarette devices, e-liquid formulations and flavour use is increasing. Here, we describe a multiple test matrix and <em>in<!--> <!-->vitro</em> approach to assess the biological impact of differing e-cigarette activation mechanism (button vs. puff-activated) and heating technology (cotton vs. ceramic wick). The e-liquids selected for each device contained the same nicotine concentration and flavourings. We tested both e-liquid and aqueous extract of e-liquid aerosol using a high throughput cytotoxicity and genotoxicity screen. We also conducted whole aerosol assessment both in a reconstituted human airway lung tissue (MucilAir) with associated endpoint assessment (cytotoxicity, TEER, cilia beat frequency and active area) and an Ames whole aerosol assay with up to 900 consecutive undiluted puffs. Following this testing it is shown that the biological impact of these devices is similar, taking into consideration the limitations and capturing efficiencies of the different testing matrices. We have contextualised these responses against previous published reference cigarette data to establish the comparative reduction in response consistent with reduced risk potential of the e-cigarette products tested in this study as compared to conventional cigarettes.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100150"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000033/pdfft?md5=4e092ed55a75181fa32f780895b7e5fe&pid=1-s2.0-S2666027X24000033-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139480197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of estrogen receptor agonists among hydroxylated polychlorinated biphenyls using classification-based quantitative structure–activity relationship models","authors":"Lukman K. Akinola ,&nbsp;Adamu Uzairu ,&nbsp;Gideon A. Shallangwa ,&nbsp;Stephen E. Abechi ,&nbsp;Abdullahi B. Umar","doi":"10.1016/j.crtox.2024.100158","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100158","url":null,"abstract":"<div><p>Identification of estrogen receptor (ER) agonists among environmental toxicants is essential for assessing the potential impact of toxicants on human health. Using 2D autocorrelation descriptors as predictor variables, two binary logistic regression models were developed to identify active ER agonists among hydroxylated polychlorinated biphenyls (OH-PCBs). The classifications made by the two models on the training set compounds resulted in accuracy, sensitivity and specificity of 95.9 %, 93.9 % and 97.6 % for ERα dataset and 91.9 %, 90.9 % and 92.7 % for ERβ dataset. The areas under the ROC curves, constructed with the training set data, were found to be 0.985 and 0.987 for the two models. Predictions made by models I and II correctly classified 84.0 % and 88.0 % of the test set compounds and 89.8 % and 85.8% of the cross-validation set compounds respectively. The two classification-based QSAR models proposed in this paper are considered robust and reliable for rapid identification of ERα and ERβ agonists among OH-PCB congeners.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100158"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000112/pdfft?md5=aaea4139aa15cb5789aef7803b3c55c3&pid=1-s2.0-S2666027X24000112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139985348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese in autism spectrum disorder and attention deficit hyperactivity disorder: The state of the art","authors":"Michael Aschner ,&nbsp;Airton C. Martins ,&nbsp;Gustavo H. Oliveira-Paula ,&nbsp;Anatoly V. Skalny ,&nbsp;Irina P. Zaitseva ,&nbsp;Aaron B. Bowman ,&nbsp;Anatoly A. Kirichuk ,&nbsp;Abel Santamaria ,&nbsp;Yousef Tizabi ,&nbsp;Alexey A. Tinkov","doi":"10.1016/j.crtox.2024.100170","DOIUrl":"10.1016/j.crtox.2024.100170","url":null,"abstract":"<div><p>The objective of the present narrative review was to synthesize existing clinical and epidemiological findings linking manganese (Mn) exposure biomarkers to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), and to discuss key pathophysiological mechanisms of neurodevelopmental disorders that may be affected by this metal. Existing epidemiological data demonstrated both direct and inverse association between Mn body burden and ASD, or lack of any relationship. In contrast, the majority of studies revealed significantly higher Mn levels in subjects with ADHD, as well as direct relationship between Mn body burden with hyperactivity and inattention scores in children, although several studies reported contradictory results. Existing laboratory studies demonstrated that impaired attention and hyperactivity in animals following Mn exposure was associated with dopaminergic dysfunction and neuroinflammation. Despite lack of direct evidence on Mn-induced neurobiological alterations in patients with ASD and ADHD, a plethora of studies demonstrated that neurotoxic effects of Mn overexposure may interfere with key mechanisms of pathogenesis inherent to these neurodevelopmental disorders. Specifically, Mn overload was shown to impair not only dopaminergic neurotransmission, but also affect metabolism of glutamine/glutamate, GABA, serotonin, noradrenaline, thus affecting neuronal signaling. In turn, neurotoxic effects of Mn may be associated with its ability to induce oxidative stress, apoptosis, and neuroinflammation, and/or impair neurogenesis. Nonetheless, additional detailed studies are required to evaluate the association between environmental Mn exposure and/or Mn body burden and neurodevelopmental disorders at a wide range of concentrations to estimate the potential dose-dependent effects, as well as environmental and genetic factors affecting this association.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100170"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000239/pdfft?md5=ef102019acae5357af36df505014d6c1&pid=1-s2.0-S2666027X24000239-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140785269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicokinetics of a developmental toxicity test in zebrafish embryos and larvae: Relationship with drug exposure in humans and other mammals","authors":"Tasuku Nawaji ,&nbsp;Naohiro Mizoguchi ,&nbsp;Ryuta Adachi ,&nbsp;Hiroki Teraoka","doi":"10.1016/j.crtox.2024.100187","DOIUrl":"10.1016/j.crtox.2024.100187","url":null,"abstract":"<div><p>To study the effects of drugs on embryo/fetal development (EFD), developmental and reproductive toxicity studies in zebrafish (<em>Danio rerio</em>) embryos is expected to be an accepted alternative method to animal studies using mammals. However, there is a lack of clarity in the relationship between the concentration of developmental toxicity agents in whole embryos or larvae (Ce) and that in aqueous solution (Cw), and also between the amount of drug exposure required to cause developmental toxicity in zebrafish embryos or larvae and that required in mammals. Here, we measured Ce for developmental toxicity agents every 24 h starting at 24 h post fertilization (hpf). We found a high correlation (<em>R</em>²: 0.87–0.96) between log [Ce/Cw] and the <em>n</em>-octanol–water distribution coefficient at pH 7 (logD) of each drug at all time points up to 120 hpf. We used this relationship to estimate the Ce values of the 21 positive-control reference drugs listed in ICH guidelines on reproductive and developmental toxicity studies (ICH S5). We then calculated the area under the Ce–time curve in zebrafish (zAUC) for each drug from the regression equation between log [Ce/Cw] and logD and compared it with the AUC at the no-observed-adverse-effect level in rats and rabbits and at the effective dose in humans described in ICH S5. The log of the calculated zAUC for the 14 drugs identified as positive in the zebrafish developmental toxicity test was relatively highly positively correlated with the log [AUC] for rats, rabbits, and humans. These findings provide important and positive information on the applicability of the zebrafish embryo developmental toxicity test as an alternative method of EFD testing. (267 words)</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"7 ","pages":"Article 100187"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000409/pdfft?md5=e51bc51b975b612fc02cfa0805c6d807&pid=1-s2.0-S2666027X24000409-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141623724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cigarette smoking inhibits myoblast regeneration by promoting proteasomal degradation of NPAT protein and hindering cell cycle progression","authors":"Jianfeng Wang ,&nbsp;Jinling Liu ,&nbsp;Jingjing Shao ,&nbsp;Hongyu Chen ,&nbsp;Luyun Cui ,&nbsp;Pei Zhang ,&nbsp;Yinan Yao ,&nbsp;Jianying Zhou ,&nbsp;Zhang Bao","doi":"10.1016/j.crtox.2024.100161","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100161","url":null,"abstract":"<div><p>Cigarette smoking (CS) causes skeletal muscle dysfunction, leading to sarcopenia and worse prognosis of patients with diverse systemic diseases. Here, we found that CS exposure prevented C2C12 myoblasts proliferation in a dose-dependent manner. Immunoblotting assays verified that CS exposure promoted the expression of cell cycle suppressor protein p21. Furthermore, CS exposure significantly inhibited replication-dependent (RD) histone transcription and caused S phase arrest in the cell cycle during C2C12 proliferation. Mechanistically, CS deregulated the expression levels of Nuclear Protein Ataxia-Telangiectasia Locus (NPAT/p220). Notably, the proteasome inhibitor MG132 was able to reverse the expression of NPAT in myoblasts, implying that the degradation of CS-mediated NPAT is proteasome-dependent. Overexpression of NPAT also rescued the defective proliferation phenotype induced by CS in C2C12 myoblasts. Taken together, we suggest that CS exposure induces NPAT degradation in C2C12 myoblasts and impairs myogenic proliferation through NPAT associated proteasomal-dependent mechanisms. As an application of the proteasome inhibitor MG132 or overexpression of NPAT could reverse the impaired proliferation of myoblasts induced by CS, the recovery of myoblast proliferation may be potential strategies to treat CS-related skeletal muscle dysfunction.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100161"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000148/pdfft?md5=62b76c5eac046a7203d59ddece106329&pid=1-s2.0-S2666027X24000148-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140062871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perfluorooctanesulfonic acid (PFOS) disrupts cadherin-16 in the developing rat thyroid gland","authors":"Nichlas Davidsen,&nbsp;Louise Ramhøj,&nbsp;Anne-Sofie Ravn Ballegaard,&nbsp;Anna Kjerstine Rosenmai,&nbsp;Cecillie Sofie Henriksen,&nbsp;Terje Svingen","doi":"10.1016/j.crtox.2024.100154","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100154","url":null,"abstract":"<div><p>Perfluorooctanesulfonic acid (PFOS) can disrupt the thyroid hormone (TH) system in rodents, potentially affecting perinatal growth and neurodevelopment. Some studies also suggest that gestational exposure to PFOS can lead to lower TH levels throughout life, indicating that PFOS may compromise thyroid gland development. To address this question, we utilized a rat thyroid gland <em>ex vivo</em> culture system to study direct effects of PFOS on the developing thyroid. No significant changes to follicular structure or size were observed with 1 µM or 10 µM PFOS exposure. However, the transcription factor <em>Foxe1</em>, together with <em>Tpo</em> and <em>Lrp2</em>, were upregulated<em>,</em> whereas the key transcription factor <em>Pax8</em> and its downstream target gene <em>Cdh16</em> were significantly downregulated at the transcript level, observed with both RT-qPCR and RNAscope. Notably, <em>Cdh16</em> expression was not uniformly downregulated across <em>Cdh16</em>-postive cells, but instead displayed a patchy expression pattern across the thyroid gland. This is a significant change in expression pattern compared to control thyroids where <em>Cdh16</em> is expressed relatively uniformly<em>.</em> The disrupted expression pattern was also seen at the protein level. This suggests that PFOS exposure can impact follicular growth and structure. Compromised follicle integrity, if irreversible, could help explain reduced TH synthesis postnatally. This view is supported by observed changes to <em>Tpo</em> and <em>Lrp2</em> expression, two factors that play a role in TH synthesis.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100154"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000070/pdfft?md5=d6bb075a4f229d5e54f3b2d446c18f78&pid=1-s2.0-S2666027X24000070-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139710242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thallium - poisoner’s poison: An overview and review of current knowledge on the toxicological effects and mechanisms","authors":"Junko Fujihara ,&nbsp;Naoki Nishimoto","doi":"10.1016/j.crtox.2024.100157","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100157","url":null,"abstract":"<div><p>Thallium (Tl) is one of the most toxic metals and its historic use in homicides has led it to be known as “the poisoner’s poison.” This review summarizes the methods for identifying Tl and determining its concentrations in biological samples in recently reported poisoning cases, as well as the toxicokinetics, toxicological effects, toxicity mechanisms, and detoxication methods of Tl. Recent findings regarding Tl neurotoxicological pathways and toxicological effects of Tl during pregnancy are also presented. Confirmation of elevated Tl concentrations in blood, urine, or hair is indispensable for diagnosing Tl poisoning. The kidneys show the highest Tl concentration within 24 h after ingestion, while the brain shows the highest concentration thereafter. Tl has a very slow excretion rate due to its large distribution volume. Following acute exposure, gastrointestinal symptoms are observed at an early stage, and neurological dysfunction is observed later: Tl causes the most severe damage in the central nervous system. Alopecia and Mees’ lines in the nails are observed within 1 month after Tl poisoning. The toxicological mechanism of Tl is considered to be interference of vital potassium-dependent processes with Tl⁺ because its ionic radius is similar to that of K⁺, as well as inhibition of enzyme reactions by the binding of Tl to -SH groups, which disturbs vital metabolic processes. Tl toxicity is also related to reactive oxygen species generation and mitochondrial dysfunction. Prussian blue is the most effective antidote, and metallothionein alone or in combination with Prussian blue was recently reported to have cytoprotective effects after Tl exposure. Because Tl poisoning cases are still reported, early determination of Tl in biological samples and treatment with an antidote are essential.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100157"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000100/pdfft?md5=dea530e23f74f5e31d09569b835173db&pid=1-s2.0-S2666027X24000100-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139935588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of in vitro biotransformation of tris (1-chloro-2-propyl) phosphate and confirmation in human urine","authors":"Fatima den Ouden ,&nbsp;Andrea Estévez-Danta ,&nbsp;Lidia Belova ,&nbsp;Celine Gys ,&nbsp;Anna Klimowska ,&nbsp;Maarten Roggeman ,&nbsp;Natan Van Wichelen ,&nbsp;José Benito Quintana ,&nbsp;Rosario Rodil ,&nbsp;Giulia Poma ,&nbsp;Adrian Covaci","doi":"10.1016/j.crtox.2024.100164","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100164","url":null,"abstract":"<div><p>Tris (1-chloro-2-propyl) phosphate (TCIPP) is one of the major organophosphate flame retardants present in the indoor and outdoor environment. Knowledge of biotransformation pathways is important to elucidate potential bioavailability and toxicity of TCIPP and to identify relevant biomarkers. This study aimed to identify TCIPP metabolites through <em>in vitro</em> human metabolism assays and finally to confirm these findings in urine samples from an occupationally exposed population to propose new biomarkers to accurately monitor exposure to TCIPP.</p><p>TCIPP was incubated with human liver microsomes and human liver cytosol to identify Phase I and Phase II metabolites, by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Using a suspect-screening approach, the established biomarkers bis (1-chloro-2-propyl) hydrogen phosphate (BCIPP) and 1-hydroxy-2-propyl bis (1-chloro-2-propyl) phosphate (BCIPHIPP) were identified. In addition, carboxyethyl bis (1-chloro-2-propyl) phosphate (TCIPP-M1), bis (1-chloropropan-2-yl) (-oxopropan-2-yl) phosphate (TCIPP-M2) and 1-chloro-3-hydroxypropan-2-yl bis (1-chloropropan-2-yl) phosphate (TCIPP-M3) were identified. TCIPP-M2, an intermediate product, was not reported before in literature. In urine samples, apart from BCIPP and BCIPHIPP, TCIPP-M1 and TCIPP-M3 were identified for the first time. Interestingly, BCIPP showed the lowest detection frequency, likely due to the poor sensitivity for this compound. Therefore, TCIPP-M1 and TCIPP-M3 could serve as potential additional biomarkers to more efficiently monitor TCIPP exposure in humans.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100164"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000173/pdfft?md5=93edeb407f8b80274045e09c6485a17a&pid=1-s2.0-S2666027X24000173-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sunitinib malate induces cell death in adult human cardiac progenitor cells","authors":"Robert Walmsley ,&nbsp;Derek S. Steele ,&nbsp;Sotiris Papaspyros ,&nbsp;Andrew J. Smith","doi":"10.1016/j.crtox.2024.100167","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100167","url":null,"abstract":"<div><p>Sunitinib malate is known to cause cardiotoxicity in a sub-population of patients, with heart failure seen in more severe cases. Cardiac progenitor cells (CPCs) have been identified in adult human myocardium and contribute to overall tissue maintenance, with previous work identifying negative impacts of sunitinib on these cells. This study aimed to characterise the toxic effects of sunitinib in human CPCs, applying sunitinib concentrations equivalent to clinical plasma levels to these cells <em>in vitro</em>. Cell viability was reduced by 26.5 ± 6.6 % by 2 μM sunitinib for 24 h (<em>p</em> &lt; 0.01); this concentration also induced fold-change increases in gene expression of: calpain (3.1 ± 0.73, <em>p</em> &lt; 0.05), FAS (2.3 ± 0.8, <em>p</em> &lt; 0.05) and BAX (1.9 ± 0.2, <em>p</em> &lt; 0.05), and a decrease in BCL-2 (3.5 ± 0.0, <em>p</em> &lt; 0.001), <em>vs</em>. control (1.0 ± 0.0). This was affirmed by sunitinib inducing fold changes in protein expression of: calpain-1 (2.5 ± 0.5, <em>p</em> &lt; 0.05); FAS receptor (2.1 ± 0.2, <em>p</em> &lt; 0.05) and BAX (2.1 ± 0.2, <em>p</em> &lt; 0.05) <em>vs</em>. control (1.0 ± 0.0). These results indicated that sunitinib induced apoptosis in CPCs, but negative annexin V staining and lack of protection by caspase inhibitors indicated this was not the cell death pathway activated. Further investigation found sunitinib was concentrated in the lysosomes and autophagosomes within CPCs, but did not induce accumulation of acidic organelles. In conclusion, these data confirm that cell death is caused by sunitinib in CPCs at concentrations equivalent to clinical plasma levels, inducing cell death pathway signals that lead to non-apoptotic cell death.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100167"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000203/pdfft?md5=4e2738196d2fda4a1c0103db46288bc7&pid=1-s2.0-S2666027X24000203-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing the effects of three neonicotinoids on embryogenesis of the South African clawed frog Xenopus laevis","authors":"Hannah Flach ,&nbsp;Carla Brendler ,&nbsp;Martina Schöpf,&nbsp;Lilly Xu,&nbsp;Julia Schneider,&nbsp;Kathrin Dewald,&nbsp;Petra Dietmann,&nbsp;Michael Kühl,&nbsp;Susanne J. Kühl","doi":"10.1016/j.crtox.2024.100169","DOIUrl":"https://doi.org/10.1016/j.crtox.2024.100169","url":null,"abstract":"<div><p>Neonicotinoids (NEOs) are widely used insecticides that are ubiquitous in agricultural use. Since NEOs are found in natural waters as well as in tap water and human urine in regions where NEOs are widely used, NEOs pose a potential hazard to non-target organisms such as animals and humans. Some of the commonly detected NEOs are imidacloprid (IMD), thiamethoxam (TMX), and its metabolite clothianidin (CLO). Although previously published scientific information, including an assessment of the environmental risks, particularly for bees, had resulted in a ban on the outdoor use of these three NEOs in the EU – their use is now only permitted in closed greenhouses – these NEOs continue to be used in agriculture in many other parts of the world. Therefore, a detailed study and comparison of the effects of NEOs on the embryonic development of non-target organisms is needed to further define the risk profiles.</p><p>Embryos of the South African clawed frog <em>Xenopus laevis</em>, a well-established aquatic model, were exposed to different concentrations of IMD, TMX, or CLO (0.1–100 mg/L) to study and compare the possible effects of a single contaminant in natural water bodies on early embryogenesis. The results included a reduced body length, a smaller orbital space, impaired cranial cartilage and nerves, and an altered heart structure and function. At the molecular level, NEO exposure partially resulted in an altered expression of tissue-specific factors, which are involved in eye, cranial placode, and heart development<em>.</em></p><p>Our results suggest that the NEOs studied negatively affect the embryonic development of the non-target organism <em>X. laevis</em>. Since pesticides, especially NEOs, pollute the environment worldwide, it is suggested that they are strictly controlled and monitored in the areas where they are used. In addition, the question arises as to whether pesticide metabolites also pose a risk to the environment and need to be investigated further so that they can be taken into account when registering ingredients.</p></div>","PeriodicalId":11236,"journal":{"name":"Current Research in Toxicology","volume":"6 ","pages":"Article 100169"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666027X24000227/pdfft?md5=638dfdd1ee6da1222c6310f335755964&pid=1-s2.0-S2666027X24000227-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140643963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}