Regulatory Toxicology and Pharmacology最新文献_第6页

Real-world safety of fruquininib in refractory metastatic colorectal cancer: A cross-database study fruquininib治疗难治性转移性结直肠癌的实际安全性：一项跨数据库研究

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-25 DOI: 10.1016/j.yrtph.2025.105973

Qian Guo , Meirong Shan , Yanhua Fu , Ni Li , Chu Wu , Wei Gao

{"title":"Real-world safety of fruquininib in refractory metastatic colorectal cancer: A cross-database study","authors":"Qian Guo , Meirong Shan , Yanhua Fu , Ni Li , Chu Wu , Wei Gao","doi":"10.1016/j.yrtph.2025.105973","DOIUrl":"10.1016/j.yrtph.2025.105973","url":null,"abstract":"<div><div>This study utilized real-world data from the U.S. FDA Adverse Event Reporting System and the WHO VigiAccess database to identify and characterize safety signals associated with fruquintinib, providing insights for clinical practice and regulatory decision-making. Through a retrospective analysis of adverse event (AE) reports for fruquintinib from these two databases, disproportionality analysis methods such as the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) were employed to detect potential pharmacovigilance signals, with cross-database consistency evaluated. The analysis revealed 4641 and 3909 AEs associated with fruquintinib in the FAERS and VigiAccess databases, respectively. The study identified several AEs not currently documented in the drug label, including dysphonia and pain. In the FAERS database, significant signals were detected in systems not covered by the label, such as blood and lymphatic, psychiatric, immune, reproductive, and ear disorders. Other unreported signals included myelosuppression, headache, dizziness, and dyspnea. In conclusion, this study not only confirmed known adverse reactions to fruquintinib but also uncovered several potential new safety signals. These findings underscore the importance of ongoing post-marketing safety monitoring to optimize the drug's risk-benefit profile. The results provide critical safety information for clinicians managing refractory metastatic colorectal cancer with fruquintinib, supporting more vigilant patient management.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105973"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145424549","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}

引用次数: 0

Serial blood collection in anaesthetised rats: Enhancing animal welfare without the need for jugular vein catheterisation 麻醉大鼠连续采血：提高动物福利，无需颈静脉置管。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-11-11 DOI: 10.1016/j.yrtph.2025.105988

Yanzhe Xu, Yun Zhu, Jianyang Lin, Jürgen Borlak

{"title":"Serial blood collection in anaesthetised rats: Enhancing animal welfare without the need for jugular vein catheterisation","authors":"Yanzhe Xu, Yun Zhu, Jianyang Lin, Jürgen Borlak","doi":"10.1016/j.yrtph.2025.105988","DOIUrl":"10.1016/j.yrtph.2025.105988","url":null,"abstract":"<div><div>Serial blood collection is a key requirement for pharmacological and toxicological studies in rodents, but existing approaches such as tail vein, retro-orbital, or catheter-based sampling are constrained by limited sample volume, variability, and welfare concerns. We developed a percutaneous technique for serial blood sampling from the external jugular vein in male Wistar rats under isoflurane anaesthesia. The method was evaluated over 14 days by monitoring body weight, behaviour, haematological and clinical chemistry parameters in a preclinical safety study at a No-Observable-Adverse-Effect-Level dose setting. Rats tolerated repeated sampling without distress, skin lesions, or behavioural abnormalities. Isoflurane induction was rapid and uneventful, and blood samples (0.5–1 ml) were consistently obtained within 2 min. Body weight changes were minimal across sessions (1.2 % after the first to 0.2 % after the sixth), indicating procedural adaptation. Haematological values remained within reference ranges, with only a significant reduction in RDW-CV, while biochemical parameters including AST, CK, and lipids showed no significant alterations; minor, non-adverse trends included reduced ALT (p < 0.041) and non-significant cholesterol and minimal non-significant increases in plasma creatinine. This study establishes repeated percutaneous jugular vein puncture as a minimally invasive, welfare-compliant, and reliable method for longitudinal blood sampling in anaesthetised rats without catheterisation, supporting robust preclinical research.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105988"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513679","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}

引用次数: 0

Evaluation of 13-week repeated-dose oral toxicity of zirconium(IV) butoxide in Crl:CD(SD) rats 丁二氧化锆（IV）对CD（SD）大鼠13周重复剂量口服毒性评价。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-21 DOI: 10.1016/j.yrtph.2025.105968

Yasumasa Murata , Jun-ichi Akagi , Yuko Doi , Takako Iso , Takaaki Umano , Kenichi Masumura , Mariko Matsumoto , Takeshi Toyoda , Kumiko Ogawa

{"title":"Evaluation of 13-week repeated-dose oral toxicity of zirconium(IV) butoxide in Crl:CD(SD) rats","authors":"Yasumasa Murata , Jun-ichi Akagi , Yuko Doi , Takako Iso , Takaaki Umano , Kenichi Masumura , Mariko Matsumoto , Takeshi Toyoda , Kumiko Ogawa","doi":"10.1016/j.yrtph.2025.105968","DOIUrl":"10.1016/j.yrtph.2025.105968","url":null,"abstract":"<div><div>Zirconium(IV) butoxide (ZB; CAS 1071-76-7) is widely used in industrial applications as a catalyst, stabilizer, and precursor for ceramic materials utilized in medical devices such as artificial bones and teeth. Metal alkoxide compounds, including ZB, are easily hydrolyzed, polymerized, and precipitated in aqueous environments. Although a no-observed-adverse-effect level (NOAEL) for ZB has been estimated by extrapolating its hydrolysis product, 1-butanol, ZB toxicological profile remains unclear, leaving data gaps for risk evaluation. In this study, we developed a method for ZB preparation and administration using corn oil as vehicle, in which ZB was retained its polymerizable form. A 13-week repeated-dose oral toxicity study was conducted in 6-week-old Crl:CD(SD) rats. Groups of ten males and females were orally administered ZB at doses of 0 (vehicle: corn oil), 100, 300, and 1000 mg/kg body weight (bw)/day, or 1-butanol at 116 mg/kg bw/day, which was equivalent to its level after dosing ZB at 1000 mg/kg bw/day. No toxicologically significant effects were observed after ZB administration. The NOAEL for ZB was estimated to be 1000 mg/kg bw/day in both sexes. These results provide essential toxicological data for safety assessment and regulatory evaluation of ZB.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105968"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355834","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}

引用次数: 0

Comprehensive study of radon levels, health risks, and physiochemical properties in tap water consumed in Iraqi Kurdistan using solid-state nuclear track detectors 使用固态核径迹探测器对伊拉克库尔德斯坦饮用自来水中的氡水平、健康风险和理化性质进行全面研究。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-10 DOI: 10.1016/j.yrtph.2025.105960

Hiwa Mohammad Qadr , Najeba Farhad Salih , Alla Ahmed Muhamad Amin

{"title":"Comprehensive study of radon levels, health risks, and physiochemical properties in tap water consumed in Iraqi Kurdistan using solid-state nuclear track detectors","authors":"Hiwa Mohammad Qadr , Najeba Farhad Salih , Alla Ahmed Muhamad Amin","doi":"10.1016/j.yrtph.2025.105960","DOIUrl":"10.1016/j.yrtph.2025.105960","url":null,"abstract":"<div><div>Water quality assessment represents a fundamental component of public health surveillance programs. Radon concentrations in potable water constitute a significant contributor to environmental contamination and radiological exposure pathways. Consequently, this investigation quantified radon concentrations in tap water samples collected from the Ranya region of Iraqi Kurdistan, utilizing passive detection methodology employing CR-39 solid-state nuclear track detectors. Radiological safety and physicochemical properties of the tap water were evaluated. Measured radon concentrations exhibited a range of 0.068–0.194 Bq L<sup>−1</sup>, with a mean of 0.107 Bq L<sup>−1</sup>. All concentrations remained substantially below established regulatory thresholds of 11.1 Bq L<sup>−1</sup> for USEPA and 100 Bq L<sup>−1</sup> for WHO guidelines. In addition, the maximum annual effective doses from <sup>222</sup>Rn ingestion were 4.143, 4.888, and 8.167 μSv y<sup>−1</sup> for adults, children, and infants, respectively. Children and adults received lower annual effective doses than infants, though all age groups remained well below the WHO safety threshold of 100 μSv y<sup>−1</sup>. Cancer risk estimates for all age groups also remained below global reference levels. A strong positive correlation was not found between <sup>222</sup>Rn levels and tap water parameters. It appears that the results dispel local fears of significant radioactive risks by showing that radon concentrations are within the limits set by international organizations.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105960"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280764","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}

引用次数: 0

Application of error-corrected sequencing technologies for in vivo regulatory mutagenicity assessment 纠错测序技术在体内调控致突变性评估中的应用。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-11-08 DOI: 10.1016/j.yrtph.2025.105985

Carole L. Yauk , Anthony M. Lynch , Vasily N. Dobrovolsky , Maik Schuler , Stephanie L. Smith-Roe , Devon Fitzgerald , Jake Higgins , Naveed Honarvar , Frank Le Curieux , Shoji Matsumura , Sheroy Minocherhomji , Leslie Recio , Jesse J. Salk , Kei-ichi Sugiyama , Takayoshi Suzuki , John W. Wills , Francesco Marchetti

{"title":"Application of error-corrected sequencing technologies for in vivo regulatory mutagenicity assessment","authors":"Carole L. Yauk , Anthony M. Lynch , Vasily N. Dobrovolsky , Maik Schuler , Stephanie L. Smith-Roe , Devon Fitzgerald , Jake Higgins , Naveed Honarvar , Frank Le Curieux , Shoji Matsumura , Sheroy Minocherhomji , Leslie Recio , Jesse J. Salk , Kei-ichi Sugiyama , Takayoshi Suzuki , John W. Wills , Francesco Marchetti","doi":"10.1016/j.yrtph.2025.105985","DOIUrl":"10.1016/j.yrtph.2025.105985","url":null,"abstract":"<div><div>Error-corrected sequencing (ECS) is a transformative method for <em>in vivo</em> mutagenicity assessment, enabling direct, highly sensitive measurement of mutation frequency and spectrum. ECS addresses key limitations of the transgenic rodent (TGR) assay, including lack of integration into standard toxicity studies, restricted model availability, and limited alignment with the 3R principles. To support regulatory acceptance, an expert workgroup of the International Workshops on Genotoxicity Testing (IWGT) reviewed ECS technologies and developed consensus recommendations for its inclusion into Organisation for Economic Co-operation and Development (OECD) test guidelines. The working group agreed that ECS: produces results that are concordant with validated TGR assays; can be incorporated into standard ≥28-day repeat-dose toxicity studies; and, data interpretation should be based on overall mutation frequency compared with concurrent vehicle controls. The working group emphasized harmonized data reporting aligned with OECD principles and endorsed study designs that enable quantitative risk assessment. Overall, the working group agreed that ECS offers a significant advancement over current mutagenicity assays by enabling the use of diverse models beyond conventional TGR systems described in OECD test guideline 488. The working group fully supports the application of ECS to generate <em>in vivo</em> mutagenicity data for regulatory submissions and recommends its inclusion in future OECD test guidelines.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105985"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490177","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}

引用次数: 0

Retraction notice to “Acute and sub-acute toxicological evaluation of lyophilized Nymphaea x rubra Roxb. ex Andrews rhizome extract” [Regul. Toxicol. Pharm. 88 (2017) 12–21] “冻干锦花的急性和亚急性毒理学评价”撤回通知。前安德鲁斯根茎提取物”[Regul。Toxicol。医药，88(2017)12-21。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-11-03 DOI: 10.1016/j.yrtph.2025.105981

Kushal Kumar , Sabeena Sharma , Ashish Kumar , Pushpender Bhardwaj , Kalpana barhwal , Sunil Kumar Hota (Scientist ‘D’)

引用次数: 0

Using read-across to identify isobutylparaben as an endocrine disruptor 使用读取识别对羟基苯甲酸异丁酯为内分泌干扰物。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-13 DOI: 10.1016/j.yrtph.2025.105965

Hanna KL. Johansson, Anna Kjerstine Rosenmai, Julie Boberg, Monica K. Draskau, Marie Louise Holmer, Terje Svingen, Marta Axelstad

引用次数: 0

Enhancing pesticide risk assessment processes at the US Environmental Protection Agency 加强美国环境保护署的农药风险评估程序。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-26 DOI: 10.1016/j.yrtph.2025.105959

Gina M. Hilton , Penelope A. Fenner-Crisp , William L. Jordan , Amy J. Clippinger , Douglas C. Wolf

引用次数: 0

Evaluating the ability of defined approaches to predict the human skin sensitisation potential of chemicals previously untested in new approach methodologies 评估已定义的方法预测以前未在新方法方法中测试的化学品的人体皮肤致敏潜力的能力。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-13 DOI: 10.1016/j.yrtph.2025.105963

Martyn L. Chilton , Tasha Jones , Adrian Fowkes , Donna S. Macmillan , Darren Kidd

{"title":"Evaluating the ability of defined approaches to predict the human skin sensitisation potential of chemicals previously untested in new approach methodologies","authors":"Martyn L. Chilton , Tasha Jones , Adrian Fowkes , Donna S. Macmillan , Darren Kidd","doi":"10.1016/j.yrtph.2025.105963","DOIUrl":"10.1016/j.yrtph.2025.105963","url":null,"abstract":"<div><div>Much progress has been made in the development and validation of New Approach Methodologies (NAMs) for assessing skin sensitisation, as part of the global move away from animal testing. While there are now numerous <em>in silico</em> models and <em>in chemico/in vitro</em> assays available, none are currently thought to be a one-for-one replacement for the animal tests, but rather several NAMs are combined within a Defined Approach (DA), such as those described in OECD guideline 497. In this study, 22 chemicals were chosen which have known human sensitisation potential, but which have not previously been tested in NAMs, to the best of the authors’ knowledge. New <em>in chemico/in vitro</em> data were generated for each chemical in three assays, and this was combined with <em>in silico</em> predictions from two models to generate predictions from four DAs. The data was used to assess the performance of the individual NAMs and DAs within a less well understood area of chemical space, and to learn more about their applicability domains. The newly generated data are made available herein in the expectation that they will be useful to others who are developing and/or validating DAs which assess the risk of chemicals causing human skin sensitisation.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105963"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302959","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}

引用次数: 0

Cytotoxic effects of silver nanoparticles and non-essential metals in murine macrophages 银纳米颗粒和非必需金属对小鼠巨噬细胞的细胞毒性作用。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-11-10 DOI: 10.1016/j.yrtph.2025.105987

Andressa Glinski , Jessica Zablocki da Luz , Aliciane de Almeida Roque , Tugstênio Lima de Souza , Arandi Ginane Bezerra Junior , Carolina Camargo de Oliveira , Ciro Alberto de Oliveira Ribeiro , Francisco Filipak Neto

{"title":"Cytotoxic effects of silver nanoparticles and non-essential metals in murine macrophages","authors":"Andressa Glinski , Jessica Zablocki da Luz , Aliciane de Almeida Roque , Tugstênio Lima de Souza , Arandi Ginane Bezerra Junior , Carolina Camargo de Oliveira , Ciro Alberto de Oliveira Ribeiro , Francisco Filipak Neto","doi":"10.1016/j.yrtph.2025.105987","DOIUrl":"10.1016/j.yrtph.2025.105987","url":null,"abstract":"<div><div>Silver nanoparticles (AgNPs) are widely used in nanotechnology products. However, the health risks associated with co-exposure to these emerging contaminants and environmental pollutants, such as non-essential metals, are poorly understood. The present study aimed to investigate the cytotoxicity and toxicological interaction of AgNPs (0.36 and 3.6 μg mL<sup>−1</sup>) + lead (Pb<sup>2+</sup>, 25 and 250 μM) and AgNPs + mercury (Hg<sup>2+</sup>, 15 and 150 μM) using the macrophage cell line RAW 264.7 as a model. Effects were observed after a few hours (4 h) on NO levels, phagocytic activity, and DNA damage. Cell viability (24 h-exposure) was affected mainly by the higher concentrations of the contaminants and their mixtures, preceded by increases in NO levels and DNA damage, but without effects on ROS levels. Co-exposure potentiated some effects (ROS and NO levels and DNA damage), indicating toxicological interaction. These important findings must be further investigated, since the interaction of Pb<sup>2+</sup> and Hg<sup>2+</sup> with AgNPs from nanoproducts may impair the function of macrophages and represent a health risk for humans.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105987"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145506568","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}

引用次数: 0