Journal of Applied Toxicology最新文献

{"title":"Subchronic Toxicity Evaluation of Dietary Administration of a Fungal Biomass From Rhizomucor pusillus","authors":"Kevin Scaife,&nbsp;Kirt R. Phipps,&nbsp;Daniella Scalise,&nbsp;Olivér Polgár","doi":"10.1002/jat.4713","DOIUrl":"10.1002/jat.4713","url":null,"abstract":"<div>\u0000 \u0000 <p>Fungal-derived food products align with sustainable food supply principles and offer a sustainable and nutritious option for consumers. <i>Rhizomucor pusillus</i> strain CBS 143028 has emerged as a candidate food ingredient. Fermentation of <i>R. pusillus</i> CBS 143028 results in a mycelium biomass mainly comprising fungal proteins, cell wall components, and micronutrients. Although <i>R. pusillus</i> has a history of safe use in the production of food enzymes and in traditional fermented foods, the fungal biomass obtained after fermentation of <i>R. pusillus</i> CBS 143028 is considered a novel food and requires a thorough safety assessment. To this end, a 90-day oral toxicity study was conducted in which Wistar rats (10/sex/group) were provided diets containing 0, 100,000, 200,000, or 300,000 ppm of <i>R. pusillus</i> mycelium. Standard toxicity study parameters as given in OECD Test Guideline 408 were examined. The mean achieved dosages of <i>R. pusillus</i> mycelium were 6398, 12,738, or 19,668 mg/kg body weight/day for males and 7235, 14,949, or 22,461 mg/kg body weight/day for females in the low-, mid-, and high-dose groups, respectively. Although statistically significant differences were reported, these effects were not considered biologically relevant or test article-related due to atypical values in the control groups, the lack of a dose response relationship, or were attributed to normal biological variation. Thus, the no-observed-adverse-effect level (NOAEL) was established at 300,000 ppm (corresponding to 19,668 and 22,461 mg/kg body weight/day for males and females, respectively), the highest concentration tested.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"400-417"},"PeriodicalIF":2.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic and Chromium Induced Toxicity on Zebrafish Kidney: Mixture Effects on Oxidative Stress and Involvement of Nrf2-Keap1-ARE, DNA Repair, and Intrinsic Apoptotic Pathways","authors":"Sreejata Kamila,&nbsp;Koushik Kumar Dey,&nbsp;Ansuman Chattopadhyay","doi":"10.1002/jat.4709","DOIUrl":"10.1002/jat.4709","url":null,"abstract":"<div>\u0000 \u0000 <p>In polluted water, cooccurrences of two carcinogens, arsenic (As) and chromium (Cr), are extensively reported. Individual effects of these heavy metals have been reported in kidney of fishes, but underlying molecular mechanisms are not well established. There is no report on combined exposure of As and Cr in kidney. Thus, the present study investigated and compared individual and combined effects of As and Cr on zebrafish (<i>Danio rerio</i>) kidney treating at their environmentally relevant concentrations for 15, 30, and 60 days. Increased ROS levels, lipid peroxidation, GSH level, and decreased catalase activity implied oxidative stress in treated zebrafish kidney. Damage in histoarchitecture in treated groups was also noticed. The current study involved gene expression study of Nrf2, an important transcription factor of cellular stress responses along with its negative regulator Keap1 and downstream antioxidant genes <i>nqo1</i> and <i>ho1</i>. Results indicated activation of Nrf2-Keap1 pathway after combined exposure. Expression pattern of <i>ogg1</i>, <i>apex1</i>, <i>polb</i>, and <i>creb1</i> revealed the inhibition of base excision repair pathway in treatments. mRNA expression of tumor suppressor genes <i>p53</i> and <i>brca2</i> was also altered. Expressional alteration in <i>bax</i>, <i>bcl2</i>, <i>caspase9</i>, and <i>caspase 3</i> indicated apoptosis (intrinsic pathway) induction, which was maximum in combined group. Inhibition of DNA repair and induction of apoptosis indicated that the activated antioxidant system was not enough to overcome the damage caused by As and Cr. Overall, this study revealed additive effects of As and Cr in zebrafish kidney after chronic exposure focusing cellular antioxidant and DNA damage responses.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 3","pages":"387-399"},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicokinetic Profiles and Potential Endocrine Disruption Effects at the Reproductive Level Promoted by Siloxanes Used in Consumer Products.","authors":"Albeiro Marrugo-Padilla, Aylin Berussa Atencio-Diaz, Maria Fernanda Barros-Domínguez, Jose Daniel Guerra-Rivadeneira, Laura Valentina Hernandez-Cuesta, Leandra Marcela Viloria-Gamez","doi":"10.1002/jat.4706","DOIUrl":"https://doi.org/10.1002/jat.4706","url":null,"abstract":"<p><p>Siloxanes, commonly known as silicones, are polymeric compounds made up of silicon and oxygen atoms bonded together alternately. Within this group of substances are linear methyl-siloxanes and cyclic methyl-siloxanes, with octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) being the most produced and used industrially. Due to their versatility, high production volume, stability, and local presence in environmental matrices and biological fluids such as breast milk, fat, and plasma, siloxanes have been considered persistent organic pollutants, representing a public health problem. This represents a public health concern, especially when different investigations have reported potential endocrine effects at the reproductive level in experimental animals exposed to D4 and D5. The objective of this study was to review the potential reproductive and endocrine effects derived from siloxanes present in personal care products (PCPs). The results of the literature review confirmed that D4 and D5 were the most used siloxanes as additives in PCP because they improve the emollient properties of the cosmetic and the physical appearance of hair and skin. Similarly the toxicological effects of siloxanes, particularly D4, D5, and D6 included significant endocrine disruption, reproductive toxicity, and liver toxicity. Studies in SD and F-344 rats, commonly used to assess these effects, have shown that D4 has low estrogenic activity, binding to ER-α receptors, whereas D5 does not bind to estrogen receptors. D4 exposure has been associated with increased uterine weight and estrous cycle alterations, leading to prolonged exposure to estrogens, which raises the risk of endometrial hyperproliferation and carcinogenesis. Recent research highlights that D5 exposure disrupts follicle growth, endometrial receptivity, and steroidogenesis, resulting in infertility and hormonal imbalances, potentially causing disorders like endometriosis and increased cancer risk. Chronic exposure to D5 has been linked to the development of uterine endometrial adenocarcinoma, with higher doses further elevating this risk.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caenorhabditis elegans CYP33 Family in Eicosanoid Regulation, Xenobiotic Metabolism, Nanotoxicity and Spermatogenesis.","authors":"Sharoen Yu Ming Lim, Willone Lim, Angela Paul Peter, Yan Pan, Mustafa Alshagga, Mohammed Abdullah Alshawsh","doi":"10.1002/jat.4707","DOIUrl":"https://doi.org/10.1002/jat.4707","url":null,"abstract":"<p><p>The CYP33 family in Caenorhabditis elegans is integral to processes like xenobiotic detoxification, eicosanoid regulation, nanotoxicity response and spermatogenesis. Limited research on C. elegans CYP33 suggests its functions are similar to human CYP33, indicating conserved roles in metabolism and disease. This review examines C. elegans CYP33 enzymes, especially CYP-33E1 and CYP-33E2, and their human homologues, focusing on their roles in eicosanoid biosynthesis, xenobiotic metabolism, nanotoxicity and spermatogenesis. Understanding these enzymes enhances insights into cytochrome P450 biology, metabolism and cyp-associated diseases.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gamma-Decanolactone Increases Stress Resistance and Improves Toxicity Parameters on the Caenorhabditis elegans Alternative Model","authors":"Glaucia Maria Campos,&nbsp;Péterson Alves Santos,&nbsp;Mariana Uczay,&nbsp;Pricila Pflüger,&nbsp;Thaís Lemos Mendes,&nbsp;Jose Angel Fontenla,&nbsp;Patrícia Pereira","doi":"10.1002/jat.4705","DOIUrl":"10.1002/jat.4705","url":null,"abstract":"<div>\u0000 \u0000 <p>Gamma-decanolactone (GD) is a monoterpene compound with anticonvulsant, antiparkinsonian, and neuroprotective effects in preclinical trials. This study aimed to evaluate the toxicity and antioxidant profile of GD in silico and in the <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) experimental model. The <i>C. elegans</i> was used to determine the median lethal concentration (LC₅₀) of GD, as well as its effect on survival, development, reproduction, pharyngeal pumping, and stress resistance assays. The in silico study did not indicate hepatotoxic, cardiotoxic, or mutagenic potential to GD. It reduced the worms' survival, both at the L1 and L4 stages, in a concentration-dependent manner with an LC₅₀ value of 212.16 ± 5.56 μmol/mL. GD did not alter the development, reproduction, and pharyngeal pumping under normal experimental conditions in the three concentrations tested (25, 50, and 100 μmol/mL). In the thermal stress assay, GD did not change the survival pattern of the worms. Hydrogen peroxide (H₂O₂) reduced the survival of <i>C. elegans</i> and decreased the number of pharyngeal pumping, with these effects being reversed by GD. Also, GD presents an antioxidant activity by modulation the expression of the stress response genes such as <i>sod-3</i>, <i>ctl-1,2,3</i>, and <i>gst-4</i>. In conclusion, GD showed low toxicity in the <i>C. elegans</i> model and antioxidant profile both in the in silico study and in vivo assays.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 2","pages":"339-349"},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxic Effects of 4-Bromodiphenyl Ether (BDE-3) on Antioxidant Enzymes, Cell Viability, Histology and Biomolecules in Zebrafish Embryo-Larvae","authors":"Shiv Kumar,&nbsp;Pooja Chadha","doi":"10.1002/jat.4708","DOIUrl":"10.1002/jat.4708","url":null,"abstract":"<div>\u0000 \u0000 <p>Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants that are being used widely in industrial and consumers products such as plastics, electronics, furniture, textiles and so forth. They can undergo debromination process to form less brominated diphenyl ethers, which are bioaccumulative, more volatile and more toxic in nature. The current study was conducted to reveal the biochemical, apoptotic, histopathological, ultrastructural and biomolecular (ATR-FTIR) toxicity of 4-bromodiphenyl ether (BDE-3) in zebrafish larvae. After the 96-h LC₅₀ determination, the zebrafish embryos were exposed to sublethal concentrations of BDE-3, that is, 0.79 and 1.59 mg/L. The MDA content was found to be significantly increased in BDE-3 exposed larvae whereas the FRAP activity was found to be decreased. The catalase (CAT), glutathione-S-transferase (GST) and acetylcholinesterase (AChE) activity were observed to be significantly increased, and a decreased superoxide dismutase (SOD) activity was reported after the BDE-3 exposure in zebrafish larvae. The cell viability was reported to be decreased in zebrafish larvae after BDE-3 exposure. Histopathological and ultrastructural alterations were also observed in the BDE-3 exposed zebrafish larvae. The changes in the biomolecules such as DNA and protein were also revealed via ATR-FTIR analysis. The present investigation will help to understand the toxic nature of less brominated diphenyl ethers and could be utilised to assess environmental risk.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 2","pages":"350-360"},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-clinical safety evaluation of Yongdamsagan-tang water extract: A 13-week subchronic oral toxicity study in Sprague Dawley rats","authors":"Woo-Young Jeon,&nbsp;Chang-Seob Seo,&nbsp;Hyekyung Ha,&nbsp;Hyeun-Kyoo Shin,&nbsp;Jae-Woo Cho,&nbsp;Mee-Young Lee","doi":"10.1002/jat.4703","DOIUrl":"10.1002/jat.4703","url":null,"abstract":"<p>Despite the continued clinical application of traditional herbal medicines, scientific evidence such as toxicological safety profile of Yongdamsagan-tang water extract (YSTW) has not yet been established. The purpose of this study was to investigate the potential toxicity profile of YSTW following a 13-week repeated oral administration at various concentrations to Sprague Dawley rats. YSTW was administered orally to rats once daily at doses of 0, 1000, 2000, and 5000 mg/kg bw/day for 13 weeks. During the experimental period, there were no significant toxicological changes related to YSTW treatment. These results indicate that the administration of YSTW for 13 weeks in the rat resulted in no signs of toxicity at up to 5000 mg/kg bw/day, which was considered the no-observed-adverse-effect level.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 2","pages":"322-338"},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of oral toxicity of WS2 nanosheets to mouse intestine: Pathological injury, trace element balance, lipid profile changes, and autophagy","authors":"Xianghao Zha,&nbsp;Sihuan Luo,&nbsp;Lianghuan Wei,&nbsp;Feixing Li,&nbsp;Youwen Li,&nbsp;Yi Cao","doi":"10.1002/jat.4701","DOIUrl":"10.1002/jat.4701","url":null,"abstract":"<p>The success of graphene oxides has gained extensive research interests in developing novel 2D nanomaterials (NMs). WS₂ nanosheets (NSs) are novel transition metal-based 2D NMs, but their toxicity is unclear. In this study, we investigated the oral toxicity of WS₂ NSs to mouse intestines. Male mice were administrated with vehicles, 1, 10, or 100 mg/kg NSs via intragastric route, once a day, for 5 days. The results indicate that the NSs did not induce pathological or ultrastructural changes in intestines. There were minimal changes of trace elements that the exposure did not induce W accumulation, and only Co levels were dose-dependently increased. Lipid droplets were observed in all groups of mice, but lipidomics data indicate that WS₂ NSs only significantly decreased four lipid species, all belonging to phosphatidylcholine (PC). The levels of proteins regulating autophagic lipolysis, namely, LC3, lysosomal associated membrane protein 2 (LAMP2) and perilipin 2 (PLIN2), were increased, but it was only statistically significantly different for LC3. The results of this study suggest that repeated intragastric exposure to WS₂ NSs only induced minimal influences on pathological injury, trace element balance, autophagy, and lipid profiles in mouse intestines, indicating relatively high biocompatibility of WS₂ NSs to mouse intestine via oral route.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 2","pages":"311-321"},"PeriodicalIF":2.7,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term nanoplastics exposure contributes to impaired steroidogenesis by disrupting the hypothalamic-testis axis: Evidence from integrated transcriptome and metabolome analysis","authors":"Qian He,&nbsp;Xin Li,&nbsp;Caiyan Xie,&nbsp;Mingzhe Zhang,&nbsp;Zebin Lai,&nbsp;Yan Zhou,&nbsp;Lei Luo,&nbsp;Yunxiao Yang,&nbsp;Mengyuan Qu,&nbsp;Kunming Tian","doi":"10.1002/jat.4696","DOIUrl":"10.1002/jat.4696","url":null,"abstract":"<p>Cumulative evidence suggested that nanoplastics (NPs) cause male toxicity, but the mechanisms of which are still misty. Steroidogenesis is a key biological event that responsible for maintaining reproductive health. However, whether dysregulated steroidogenesis is involved in NPs-induced impaired male reproductive function and the underlying mechanism remains unclear. In our study, Balb/c mice were continuously exposed to pristine-NPs or NH₂-NPs for 12 weeks, spanning the puberty and adult stage. Upon the long-term NPs treatment, the hypothalamus and testis were subjected to transcriptome and metabolome analysis. And the results demonstrated that both primitive-NPs and NH₂-NPs resulted in impaired spermatogenesis and steroidogenesis, as evidenced by a significant reduction in sperm quality, testosterone, FSH, and LH. The expression of genes involved in hypothalamic-pituitary-testis (HPT) axis, such as <i>Kiss-1</i> and <i>Cyp17a1</i> that encoded the key steroid hormone synthetase, was also diminished. Furthermore, the phosphatidylcholine and pantothenic acid that mainly enriched in glycerophospholipid metabolism were significantly reduced in the testis. Comprehensive analysis of the transcriptome and metabolome indicated that down-regulated <i>Cyp17a1</i> was associated with decreased metabolites phosphatidylcholine and pantothenic acid. Overall, we speculate that the disturbed HPT axis induced by long-term NPs contributes to disordered glycerophospholipid metabolism and subsequently impaired steroidogenesis. Our findings deepen the understanding of the action of the mechanism responsible for NPs-induced male reproductive toxicology.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 2","pages":"298-310"},"PeriodicalIF":2.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotine as a female reproductive toxicant—A review","authors":"Jitender Kumar Bhardwaj,&nbsp;Anshu Siwach,&nbsp;Som Nath Sachdeva","doi":"10.1002/jat.4702","DOIUrl":"10.1002/jat.4702","url":null,"abstract":"<p>The preceding decades have seen an extensive emergence of the harmful effects of tobacco smoke on systemic health. Among the various compounds of tobacco, nicotine is one of the principal, potentially hazardous, and toxic components which is an oxidant agent that can affect both men's and women's fertility. Nicotine exerts its effect by modulating the expression of transmembrane ligand-gated ion channels called nicotinic acetylcholine receptors. The activities of female reproduction might be disrupted by exposure to nicotine at various sites, such as the ovary or reproductive tract. It's been demonstrated that nicotine might cause oxidative stress, apoptosis, hormonal imbalance, abnormalities in chromosomal segregation, impact oocyte development, and disruption in ovarian morphology and functions. This review paper summarizes the findings and provides an updated overview of the evidence on the harmful effects of nicotine use on women's reproductive health and the resulting detrimental impacts on the body. Additionally, it provides the detailed possible mechanisms involved in impairing reproductive processes like folliculogenesis, oocyte maturation, steroidogenesis, and pregnancy in different animal species.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"534-550"},"PeriodicalIF":2.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}