Regulatory Toxicology and Pharmacology最新文献_第3页

Preliminary safety risk assessment of parabens in children's cosmetics sold in China 对羟基苯甲酸酯在中国销售的儿童化妆品中的初步安全风险评估

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-30 DOI: 10.1016/j.yrtph.2025.105935

Ren Wang, Cen Chen, Qiaoyuan Cheng, Yuanyang Wu, Linqi Yan, Zhen Xie, Zehua Li, Shanshan Liu, Yongjun Lou

{"title":"Preliminary safety risk assessment of parabens in children's cosmetics sold in China","authors":"Ren Wang, Cen Chen, Qiaoyuan Cheng, Yuanyang Wu, Linqi Yan, Zhen Xie, Zehua Li, Shanshan Liu, Yongjun Lou","doi":"10.1016/j.yrtph.2025.105935","DOIUrl":"10.1016/j.yrtph.2025.105935","url":null,"abstract":"<div><div>Since adverse health outcomes of parabens added in children's cosmetics have been reported, it is important to investigate preliminary risk characteristic assessment of parabens preservatives in children's cosmetics. This study aimed to calculate exposure parameters using a combination experimental data and an exposure assessment tool to make safety assessment for parabens in children's cosmetics. The paraben concentration of different formulation types of 63 products of children's cosmetic products were measured by High Performance Liquid Chromatography. Based on product usage, paraben concentrations, exposure factors, behavioral patterns and exposure routes, the exposure parameters of parabens in children's cosmetics were calculated by mathematical mode from ConsExpo Web. A margin of safety (MoS) was calculated for safety evaluations. Results showed that 4-hydroxybenzoate methyl (MP) was the most commonly used paraben, which was used in 30.2 % of products, followed by propyl 4-hydroxybenzoate (PP) (12.7 %), ethyl 4-hydroxybenzoate (EP) and butyl 4-hydroxybenzoate (BP) both in 1.6 % of products. The concentrations of parabens in the cosmetic products were all within the safety limits required by the SCCS. The exposure to parabens decreased with increasing age in accordance with a published data. The MoS of parabens in children's cosmetics were all more than 100, indicating parabens to be of manageable risk and safe for use.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105935"},"PeriodicalIF":3.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921531","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

A new method of consistency evaluation of brain drugs: a case study of edaravone 脑药物一致性评价新方法——以依达拉奉为例。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-30 DOI: 10.1016/j.yrtph.2025.105933

Liqiang Gu , Yanping Hu , Yinfang Lai , Sheng Zhang , Haoran Wang , Xiaozhen Xu , Lingfang Chen , Yuhua Shi , Jiechao Chen , Xiaochun Sun , Yuan Zhang , Lingzhi Hu

{"title":"A new method of consistency evaluation of brain drugs: a case study of edaravone","authors":"Liqiang Gu , Yanping Hu , Yinfang Lai , Sheng Zhang , Haoran Wang , Xiaozhen Xu , Lingfang Chen , Yuhua Shi , Jiechao Chen , Xiaochun Sun , Yuan Zhang , Lingzhi Hu","doi":"10.1016/j.yrtph.2025.105933","DOIUrl":"10.1016/j.yrtph.2025.105933","url":null,"abstract":"<div><div>Bioequivalence test is typically conducted by determining the drug concentration in plasma. However, this is not suitable for brain drugs (like Edaravone) that have targets in CNS. The amount of a drug in target site in the CNS is responsible for its activity in the brain, while the concentration of a drug in the blood has a weak impact on the CNS. In this paper, a new consistency evaluation method for brain drugs was established. 16 rats were divided into two groups. One group was administered the test preparation, and the other group was administered the control preparation. Then, cerebrospinal fluid (CSF) samples were collected. All of the CSF samples were examined by LC-MS. The 90 % confidence interval of the geometric mean ratio of AUC<sub>0-t</sub> was 90.30–150.59 %, and 91.79–211.06 % for C<sub>max</sub>. In addition, the result indicated that the two preparations were not bioequivalent in the CNS, although the concentration-time profile and pharmacokinetic parameters were quite similar. The results revealed the particularity and complexity of the bioequivalence test for brain drugs that have targets in the CNS. The feasibility of the test was confirmed, and our results provide useful information for the consistency evaluation of brain drugs.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105933"},"PeriodicalIF":3.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966519","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 good review practices at the Food and Drugs Authority of Ghana as it strives to become a World Health Organization-listed agency 在加纳食品和药物管理局努力成为世界卫生组织上市机构的过程中，对其良好审查做法进行评估。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-29 DOI: 10.1016/j.yrtph.2025.105932

Mercy Owusu-Asante , Delese Mimi Darko , Seth Seaneke , Neil McAuslane , Stuart Walker , Sam Salek

{"title":"Evaluation of good review practices at the Food and Drugs Authority of Ghana as it strives to become a World Health Organization-listed agency","authors":"Mercy Owusu-Asante , Delese Mimi Darko , Seth Seaneke , Neil McAuslane , Stuart Walker , Sam Salek","doi":"10.1016/j.yrtph.2025.105932","DOIUrl":"10.1016/j.yrtph.2025.105932","url":null,"abstract":"<div><div>The aim of this study was to assess the good review practices (GRevPs) of the Food and Drugs Authority (FDA) Ghana in order to identify opportunities for improvement.</div><div>Reviewers of the FDA Ghana completed an established, structured and multi-dimensional questionnaire for the assessment of GRevPs. Twenty-seven of 30 assessors took part in the study; 70 % reported that GRevPs have been implemented and fully adopted across the authority. The three most common reasons quality measures were implemented at FDA Ghana were to be more efficient, ensure consistency, and to minimize errors. Most respondents believed that the current GRevPs framework could be improved and additional training to learn and understand how GRevPs are to be used and incorporated into daily work; 90 % reported that the FDA Ghana has a consistent method for documenting GRevPs that need improvement and a mechanism to facilitate updating. In general, the importance of GRevPs was well understood by the assessors; however, target timelines were not well followed at both the department and agency levels. This study provided a baseline for the FDA Ghana GRevP knowledge, attitudes, and practices as well as areas for improvement to work toward becoming a World Health Organization-listed authority.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105932"},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966511","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

Preclinical safety, tolerability and pharmacokinetics of a novel cyclobenzaprine hydrochloride nasal spray 新型盐酸环苯扎林鼻喷雾剂的临床前安全性、耐受性和药代动力学

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-25 DOI: 10.1016/j.yrtph.2025.105930

Chitrang R. Shah , Sudhir R. Patel , Laxit K. Bhatt , Viral I. Rajwadi , Urvit P. Patel , Hitesh Kadu , Jitendra H. Patel , Harilal Patel , Ramchandra K. Ranvir , Rajesh Sundar , Ritu N. Laddha , Mukul R. Jain

{"title":"Preclinical safety, tolerability and pharmacokinetics of a novel cyclobenzaprine hydrochloride nasal spray","authors":"Chitrang R. Shah , Sudhir R. Patel , Laxit K. Bhatt , Viral I. Rajwadi , Urvit P. Patel , Hitesh Kadu , Jitendra H. Patel , Harilal Patel , Ramchandra K. Ranvir , Rajesh Sundar , Ritu N. Laddha , Mukul R. Jain","doi":"10.1016/j.yrtph.2025.105930","DOIUrl":"10.1016/j.yrtph.2025.105930","url":null,"abstract":"<div><div>These studies examined the effects of repeated intranasal administration of Cyclobenzaprine hydrochloride in rats and dogs. In rats, doses up to 1.05 mg/animal/day over 28 days showed no mortality or toxicity. Body weight, feed intake, ophthalmological and neurobehavioral assessments, and clinical pathology evaluations remained unaffected. Microscopic examinations revealed minimal non-adverse hyperplasia at the administration site in the nasal cavity. No histopathological changes were observed in other organs or tissues, establishing the NOAEL at 1.05 mg/animal/day. In dogs, doses up to 10.5 mg/animal/day over 14 days were well-tolerated, with only mild local irritation observed as nasal itching, which resolved quickly post-dosing. Body weights, food consumption, and comprehensive neurobehavioral assessments, including ECG examinations and reflex tests, showed no adverse effects. Hematological, clinical chemistry, and urinalysis variations were minimal and non-dose-dependent. Microscopic evaluations of the nasal cavity and other anatomical structures showed mild non-adverse changes, with no significant histopathological findings in the olfactory epithelium, olfactory bulb, or brain. These findings indicate that Cyclobenzaprine Hydrochloride Nasal Spray is well-tolerated with a NOAEL of 1.05 mg/animal/day in rats and ≥10.5 mg/animal/day in dogs, suggesting potential for safe intranasal administration in clinical use.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105930"},"PeriodicalIF":3.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916770","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

Permeation studies of chlorpyrifos through skin and synthetic membranes to improve the in vitro dermal absorption assay of lipophilic compounds with ethanolic receptors 毒死蜱通过皮肤和合成膜的渗透研究，以改善具有乙醇受体的亲脂化合物的体外皮肤吸收测定

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-23 DOI: 10.1016/j.yrtph.2025.105931

Dorinda Marques-da-Silva , Margarida Franco , Cristiana Violante , Ricardo Lagoa

{"title":"Permeation studies of chlorpyrifos through skin and synthetic membranes to improve the in vitro dermal absorption assay of lipophilic compounds with ethanolic receptors","authors":"Dorinda Marques-da-Silva , Margarida Franco , Cristiana Violante , Ricardo Lagoa","doi":"10.1016/j.yrtph.2025.105931","DOIUrl":"10.1016/j.yrtph.2025.105931","url":null,"abstract":"<div><div>The <em>in vitro</em> percutaneous absorption assay is standardized, but the common use of 50 % ethanol in the receptor compartment for lipophilic compounds is questioned. In parallel, the demand for animal-free methodologies is driving the application of synthetic membranes without standardization guidelines. To address these issues, this study investigated the permeation of the lipophilic compound chlorpyrifos using different ethanol-containing receptor fluids with human and pig skin <em>ex vivo</em>, and silicone and STRAT-M® membranes. The results considered several factors, particularly chlorpyrifos solubility and the contact angles between skin models and receptor fluids. Original experimental approaches demonstrated that ethanol from the receptor rapidly crosses to the donor compartment increasing chlorpyrifos diffusivity. Compared to the described <em>in vivo</em> dermal absorption, human skin and STRAT-M® yielded the best predictive permeation parameters. However, high percentage of ethanol in the receptor fluid can lead to an overestimation of percutaneous absorption. Summing up, it is important to carefully determine the concentration of ethanol to be used in the receptor fluid of lipophilic compounds’ assays while further research with synthetic membranes is needed prior to their wider adoption.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105931"},"PeriodicalIF":3.5,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919993","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

Streamlined and accelerated nonclinical development of COVID-19 vaccines and therapeutics – an IQ consortium DruSafe survey 简化和加速COVID-19疫苗和疗法的非临床开发——IQ联盟DruSafe调查

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-21 DOI: 10.1016/j.yrtph.2025.105928

Maggie M. Liu , Sherry L. Ralston

{"title":"Streamlined and accelerated nonclinical development of COVID-19 vaccines and therapeutics – an IQ consortium DruSafe survey","authors":"Maggie M. Liu , Sherry L. Ralston","doi":"10.1016/j.yrtph.2025.105928","DOIUrl":"10.1016/j.yrtph.2025.105928","url":null,"abstract":"<div><div>The global COVID-19 pandemic had a major impact on the development of vaccines and treatments, leading to the swift creation and distribution of various medical solutions. This period reshaped many facets of drug and vaccine development, as well as the regulatory review process, fostering innovations while maintaining standards of safety, quality, and efficacy. To capture and document these innovative methods and key takeaways in nonclinical development for COVID-19 drugs and vaccines, the DruSafe Leadership Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) conducted a survey among its members with experience in developing COVID-19 treatments and preventatives. The survey captured how companies used innovative nonclinical strategies to expedite the availability of promising drugs and vaccines in response to the urgent medical need, as well as their interactions with regulatory agencies. This article presents the survey results, offering insights into nonclinical development for 15 therapeutics or vaccines submitted by 10 pharmaceutical companies. It also reflects on how these lessons can guide responses to future pandemics and/or other serious, life-threatening diseases.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105928"},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895521","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

Mode of action analysis for mouse liver tumor formation by MGK-264 and human relevance MGK-264对小鼠肝肿瘤形成的作用模式分析及其与人的相关性

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-20 DOI: 10.1016/j.yrtph.2025.105929

Junji Yano , Kensuke Kawamoto , Yukako Shimotsuma , Keiko Ogata , Kohei Matsunaga , Jun Abe , Satoki Fukunaga , Thomas G. Osimitz , Brian G. Lake , Hiroyuki Asano

{"title":"Mode of action analysis for mouse liver tumor formation by MGK-264 and human relevance","authors":"Junji Yano , Kensuke Kawamoto , Yukako Shimotsuma , Keiko Ogata , Kohei Matsunaga , Jun Abe , Satoki Fukunaga , Thomas G. Osimitz , Brian G. Lake , Hiroyuki Asano","doi":"10.1016/j.yrtph.2025.105929","DOIUrl":"10.1016/j.yrtph.2025.105929","url":null,"abstract":"<div><div>MGK-264, an insecticidal synergist, has been shown to increase the incidence of liver tumors in male and female mice. As MGK-264 is not a genotoxic compound, a series of investigative studies were conducted to elucidate the mode of action (MoA) for liver tumor production by MGK-264. Male and female CD-1 mice were given diets containing MGK-264 at 400, 3000, and 6000 ppm for 7 and/or 14 days. Treatment with MGK-264 caused activation of the constitutive androstane receptor (CAR), which resulted in liver hypertrophy, induction of cytochrome P450 CYP2B subfamily enzymes, and increased replicative DNA synthesis (RDS) in the liver in male and female mice. In contrast, these changes were not observed in the livers of male CAR and pregnane X receptor (PXR) knockout (CAR KO/PXR KO) mice treated with MGK-264. The treatment of primary human hepatocytes with 1–30 μM MGK-264 increased <em>CYP2B</em> and <em>CYP3A</em> mRNA expression, but had no effect on hepatocyte RDS. Similarly, the treatment of chimeric mice with human hepatocytes with 6000 ppm MGK-264 in the diet for 7 days resulted in increased <em>CYP2B</em> and <em>CYP3A</em> mRNA expression, but had no significant effect on human hepatocyte RDS. In summary, based on these investigative studies, MGK-264 is a CAR activator at carcinogenic dose levels in mouse liver. A robust MoA for MGK-264-induced mouse liver tumor formation has been established and is not considered plausible for humans on the basis of qualitative differences between humans and mice. This conclusion is supported by data from human epidemiology studies with CAR activators.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"163 ","pages":"Article 105929"},"PeriodicalIF":3.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902813","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

The dangerous precedent of silencing government science 压制政府科学的危险先例。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-08 DOI: 10.1016/j.yrtph.2025.105927

Martin van den Berg Prof. Dr. ((Co)Editor-in-Chief)

引用次数: 0

Corrigendum to “Acute and 28-days repeated dose sub-acute toxicity study of gallic acid in albino mice” [Regulat. Toxicol. Pharmacol. RTP 101 (2019) 71–78] 《没食子酸对白化小鼠急性和28天重复给药亚急性毒性研究》的勘误表。Toxicol。杂志。RTP 101(2019) 71-78]。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-05 DOI: 10.1016/j.yrtph.2025.105917

Bhavesh C. Variya , Anita K. Bakrania , Prem Madan , Snehal S. Patel

引用次数: 0

Matched molecular pairs-driven read-across for the prediction of genotoxicity of plant protection product residues 匹配分子对驱动的跨读预测植保产品残留的遗传毒性

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-08-04 DOI: 10.1016/j.yrtph.2025.105915

S.J. Enoch , Z. Hasarova , M.T.D. Cronin , K. Bridgwood , S. Rao , A. Hueser , F.M. Kluxen , M. Frericks

引用次数: 0