Regulatory Toxicology and Pharmacology最新文献_第6页

Global regulatory considerations and practices for tumorigenicity evaluation of cell-based therapy 细胞治疗致瘤性评估的全球监管考虑和实践。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-02-01 DOI: 10.1016/j.yrtph.2024.105769

Dehu Dou , Jing Lu , Jinhui Dou , Yan Huo , Xinjiang Gong , Xuefeng Zhang , Xijing Chen

{"title":"Global regulatory considerations and practices for tumorigenicity evaluation of cell-based therapy","authors":"Dehu Dou , Jing Lu , Jinhui Dou , Yan Huo , Xinjiang Gong , Xuefeng Zhang , Xijing Chen","doi":"10.1016/j.yrtph.2024.105769","DOIUrl":"10.1016/j.yrtph.2024.105769","url":null,"abstract":"<div><div>Cell-based therapy, as a “living drug”, possesses inherent complexity and heterogeneity. Tumorigenicity evaluation is a crucial aspect of safety assessment for cell-based therapies. Stem cell-based therapies such as hESCs and hiPSCs, may contain residual undifferentiated cells in final product, which have a high potential for proliferation and differentiation, posing a risk of tumor formation in vivo. Additionally, the source, phenotype, differentiation status, proliferative capacity, ex vivo culture conditions, ex vivo processing methods, injection site, and route of administration also influence the tumorigenicity risk of the cells. Tumorigenicity evaluation needs to consider the complexity of design and multifactorial influences. Through the analysis and summary of partial existing marketed and under-development products, combined with practical experience, it is found that there are many differences in requirements and practices related to cell tumorigenicity globally. Regulatory requirements also vary, and guidance and support for applicants’ declaration requirements in different regions need to be considered in conjunction with product characteristics and regulatory considerations. This article comprehensively summarizes the requirements of tumorigenicity from main regulatory agencies. Currently, there is no unified global regulatory consensus on technical implementation guide, measures for quantitation or standardization have not been established for evaluation systems. However, based on regulatory requirements and industry practice summaries, through literature research and analysis of tumorigenicity strategy of representative marketed products, the basic focus, and evaluation strategies for tumorigenicity assessment have been preliminarily clarified, providing a reference for the tumorigenicity design of variety of cell-based therapy products.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"156 ","pages":"Article 105769"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915356","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}

引用次数: 0

The dual endothelin A and angiotensin II type 1 receptor antagonist sparsentan (FILSPARI®) exhibits a safe nonclinical male fertility toxicity profile 双重内皮素A和血管紧张素II型1受体拮抗剂sparsentan （FILSPARI®）显示出安全的非临床男性生育毒性。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-02-01 DOI: 10.1016/j.yrtph.2024.105770

Patricia W. Bedard , Francesca Pretto , Sima Patel , Celia Jenkinson , Tacey White , Donald E. Kohan

{"title":"The dual endothelin A and angiotensin II type 1 receptor antagonist sparsentan (FILSPARI®) exhibits a safe nonclinical male fertility toxicity profile","authors":"Patricia W. Bedard , Francesca Pretto , Sima Patel , Celia Jenkinson , Tacey White , Donald E. Kohan","doi":"10.1016/j.yrtph.2024.105770","DOIUrl":"10.1016/j.yrtph.2024.105770","url":null,"abstract":"<div><div>Marketed endothelin receptor antagonists (ERAs) have been associated with testicular tubular atrophy and decreases in male animal fertility in chronic toxicity studies in rats and dogs. Consistent with these findings, reduced sperm count has been observed in the clinical setting and is considered a potential class risk with chronic administration of ERAs. In contrast, no such effects on male animal fertility are noted with angiotensin II type 1 receptor blocker (ARB) treatment. Sparsentan (FILSPARI®) is a novel single molecule dual antagonist that antagonizes both the endothelin type A and angiotensin II type 1 receptors. We explored whether the reproductive toxicology profile of this dual endothelin angiotensin antagonist is more like that of marketed ERAs or ARBs. A full package of repeat dose general toxicity, juvenile toxicity, carcinogenicity, and reproductive and developmental toxicity studies was completed with sparsentan. A thorough review of the results from these studies has shown no evidence of effects of sparsentan on spermatogenesis or testicular histopathology. The overall conclusion of this assessment is that sparsentan is not toxic to the testes or the spermatogenic process and is more like ARBs than ERAs in its male fertility toxicity profile.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"156 ","pages":"Article 105770"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915360","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}

引用次数: 0

Toxicological evaluation of vanadium and derivation of a parenteral tolerable intake value for medical devices 钒的毒理学评估和医疗器械肠外耐受摄入值的推导。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-02-01 DOI: 10.1016/j.yrtph.2024.105732

Charlotte E. Laupheimer , Yana Kolianchuk , Rex E. FitzGerald , Martin F. Wilks , Arne Jaksch

引用次数: 0

CDSCO alerts: A retrospective dosage form - Wise analysis of quality control alerts issued to pharmaceutical companies from 2018 to 2023 CDSCO警报：2018年至2023年向制药公司发布的质量控制警报的回顾性剂型分析。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-02-01 DOI: 10.1016/j.yrtph.2025.105775

Akanksha Dashawant , Richa Khadke , Amol Shete , Vinod Gaikwad

引用次数: 0

Ames mutagenicity of 15 aryl, benzyl, and aliphatic ring N-nitrosamines 15种芳基、苄基和脂肪环n -亚硝胺的Ames诱变性。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-02-01 DOI: 10.1016/j.yrtph.2024.105763

Ayako Furuhama , Kei-ichi Sugiyama , Masamitsu Honma

{"title":"Ames mutagenicity of 15 aryl, benzyl, and aliphatic ring N-nitrosamines","authors":"Ayako Furuhama , Kei-ichi Sugiyama , Masamitsu Honma","doi":"10.1016/j.yrtph.2024.105763","DOIUrl":"10.1016/j.yrtph.2024.105763","url":null,"abstract":"<div><div>The Ames mutagenicity test is an effective means of screening compounds for their carcinogenic potential. Here, we conducted Ames tests on 15 aryl, benzyl, and aliphatic ring <em>N</em>-nitrosamines. Then, by using two indicators of mutagenicity strength calculated from the Ames test results, namely, maximum specific activity (MSA; number of revertant colonies) and maximum fold increase (MFI; relative ratio of increased colonies), we examined the relationship between Ames mutagenicity strength and Carcinogenic Potency Categorization Approach (CPCA) potency category, which is a structure–activity-relationship–based prediction of the carcinogenic potency of nitrosamines. Eleven of the test compounds were Ames positive and four were negative. Of the 11 positive compounds, three were categorized as strong positive (MSA ≥1000), five as medium positive (100 ≤ MSA <1000), and three as weak positive (MSA <100). The compounds with an aliphatic ring showed a negative relationship between mutagenicity strength (i.e., MSA or MFI) and carcinogenic potential (i.e., CPCA category), whereas, the alpha-methyl aryl <em>N</em>-nitrosamines did not. Overall, <span>MSA</span> and <span>MFI</span> were found to be detailed indicators of the carcinogenic potency of the <em>N</em>-nitrosamines and can potentially be used to support CPCA categorization.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"156 ","pages":"Article 105763"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814067","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}

引用次数: 0

Incorporating Singaporean habits and practices for cosmetics and personal care products into a global consumer aggregate exposure model 将新加坡人对化妆品和个人护理产品的习惯和做法纳入全球消费者总体暴露模型。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-02-01 DOI: 10.1016/j.yrtph.2024.105752

Siti Amelia Juraimi , Cesar Scrochi , Jonathan Lok , Anne Marie Api , Benjamin P.C. Smith

{"title":"Incorporating Singaporean habits and practices for cosmetics and personal care products into a global consumer aggregate exposure model","authors":"Siti Amelia Juraimi , Cesar Scrochi , Jonathan Lok , Anne Marie Api , Benjamin P.C. Smith","doi":"10.1016/j.yrtph.2024.105752","DOIUrl":"10.1016/j.yrtph.2024.105752","url":null,"abstract":"<div><div>Understanding consumer habits and practices of cosmetics and personal care products (PCP) is essential to generate realistic product exposure data for the safety assessment of ingredients such as fragrance materials. Product usages can vary across regions due to differences in cultural norms, seasonal and climate conditions, and the availability of different product forms, yet there is limited data published on cosmetics and PCP use outside of North America and Europe. This study reports the habits and practices of cosmetics and PCP (such as frequency and amount of use) in Singapore where participants (<em>n</em> = 494, aged 21–64 years) recorded their product usages and had their products weighed over a two-week period. Overall, similar use patterns were observed across demographic groups within the Singapore population for most of the products surveyed, as were the expected usage amounts. Additionally, the Singaporean dataset was mapped onto the Creme-RIFM aggregate exposure model to assess exposure estimates. Preliminary comparisons with product exposures observed in the United States (US) and Europe suggest that exposures in Singapore are comparable. Findings from this study will contribute to the Creme-RIFM model, expanding its geographic scope and applicability for the global safety assessment of fragrance ingredients and fragranced products.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"156 ","pages":"Article 105752"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755115","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

PBT/PMT assessment of active pharmaceutical ingredients 有效药物成分的PBT/PMT评价。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-02-01 DOI: 10.1016/j.yrtph.2025.105772

Gemma Janer , Joanne Elmoznino , Andreas Häner , Irene Bramke

{"title":"PBT/PMT assessment of active pharmaceutical ingredients","authors":"Gemma Janer , Joanne Elmoznino , Andreas Häner , Irene Bramke","doi":"10.1016/j.yrtph.2025.105772","DOIUrl":"10.1016/j.yrtph.2025.105772","url":null,"abstract":"<div><div>The EU Commission proposal for a new EU pharmaceutical legislation considers PBT (persistence-bioaccumulation-toxicity) and PMT (persistence-mobility-toxicity) criteria for pharmaceuticals. Under current environmental risk assessment guidance, a PBT assessment is required regardless of the predicted environmental concentrations. However, consumption volumes of pharmaceuticals are contingent on marketing approval by EMA and are therefore predictable and their toxicological potency is established prior to any regulatory approval. Consumption volume and toxicological potency of pharmaceuticals span many orders of magnitude and are strong risk determinants. Routine data generation to evaluate persistence, mobility and bioaccumulation hazards as a means of pinpointing pharmaceuticals of increased environmental concern is therefore of questionable added value.</div><div>We present options to derive action triggers for PBT and/or PMT screening using exposure predictions and toxicological potency data. Our simulations demonstrate that an exposure-based action limit can be established as a trigger for PMT assessment, while a combined trigger based on exposure levels and mammalian toxicity is proposed for PBT assessment. The proposed approach is conservatively designed to ensure that compounds with any potential risks a) of secondary poisoning (main concern for PBT substances) and b) to groundwater/drinking water (main concern for PMT substances) are targeted for full evaluation.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"156 ","pages":"Article 105772"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010627","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}

引用次数: 0

Comprehensive extractables and leachables sensitization analysis and practical application of a risk-based approach to sensitization assessment for parenteral drug products 综合萃取物和浸出物致敏分析和基于风险的方法在肠外药物致敏评估中的实际应用。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-01-28 DOI: 10.1016/j.yrtph.2025.105776

Patricia Parris , Geraldine Whelan , Martyn L. Chilton , Claire Beaumont , Anders Burild , Uma Bruen , Courtney Callis , Jessica Graham , Natalia Kovalova , Elizabeth A. Martin , Melisa Masuda-Herrera , Carsten Worsøe , Anissa Alami , Joel Bercu , Dvir Doron , Kristen Dusenbury , Qiang Fu , Troy Griffin , Jedd Hillegass , Esther Johann , Lee Nagao

{"title":"Comprehensive extractables and leachables sensitization analysis and practical application of a risk-based approach to sensitization assessment for parenteral drug products","authors":"Patricia Parris , Geraldine Whelan , Martyn L. Chilton , Claire Beaumont , Anders Burild , Uma Bruen , Courtney Callis , Jessica Graham , Natalia Kovalova , Elizabeth A. Martin , Melisa Masuda-Herrera , Carsten Worsøe , Anissa Alami , Joel Bercu , Dvir Doron , Kristen Dusenbury , Qiang Fu , Troy Griffin , Jedd Hillegass , Esther Johann , Lee Nagao","doi":"10.1016/j.yrtph.2025.105776","DOIUrl":"10.1016/j.yrtph.2025.105776","url":null,"abstract":"<div><div>The Extractables and Leachables Safety Information Exchange (ELSIE) Consortium added to the sensitization potency analysis of Parris et al. (2023) by including the Product Quality Research Institute (PQRI) extractable and leachable dataset (Johnson et al., 2024; Product Quality Research Institute, 2021). This analysis of the comprehensive E&L dataset showed 5% of chemicals (20/407) had experimental results demonstrating or were predicted to be potent (strong or extreme) sensitizers, supporting the previous conclusion, that potent sensitizers are of low prevalence and are not routinely observed as leachables in pharmaceutical products. By accounting for prevalence of sensitization in the overall E&L dataset, the probability of any potential leachable being more potent than the less than lifetime ICH M7 (10, 20, and 120 μg/day for human exposure of >1–10 years, >1–12 months, and <1 month respectively) and non-mutagenic ELSIE threshold values (35, 110, and 180 μg/day for human exposures of >10 years to lifetime, >1–10 years, and ≤1 year respectively) (Masuda-Herrera et al., 2022) was considered. The M7 and ELSIE thresholds are anticipated to provide ≥95% coverage of induction of sensitization, supporting the use of these thresholds to set the Safety Concern Threshold (SCT).</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"157 ","pages":"Article 105776"},"PeriodicalIF":3.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066288","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}

引用次数: 0

Control performance of Amphibian Metamorphosis Assays with Xenopus laevis 非洲爪蟾防治两栖动物变态试验的效果。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2025-01-18 DOI: 10.1016/j.yrtph.2025.105773

James R. Wheeler , Raechel Puglisi , Adriana C. Bejarano , Zhenglei Gao , Laurent Lagadic , Scott Glaberman , Constance A. Mitchell , Natalie Burden , Valentin Mingo , Scott G. Lynn , Michelle R. Embry

{"title":"Control performance of Amphibian Metamorphosis Assays with Xenopus laevis","authors":"James R. Wheeler , Raechel Puglisi , Adriana C. Bejarano , Zhenglei Gao , Laurent Lagadic , Scott Glaberman , Constance A. Mitchell , Natalie Burden , Valentin Mingo , Scott G. Lynn , Michelle R. Embry","doi":"10.1016/j.yrtph.2025.105773","DOIUrl":"10.1016/j.yrtph.2025.105773","url":null,"abstract":"<div><div>The amphibian metamorphosis assay (AMA) is an <em>in vivo</em> screen to assess potential interactions of chemicals with the amphibian thyroid system. Tadpoles are exposed for 21-days, then assessed for development and growth after 7 days and at test termination. This paper presents data from studies performed to satisfy test orders from the US EPA's Endocrine Disruptor Screening Program. Data Evaluation Records were used to collate the control variability and performance of biological endpoints in AMAs conducted in different laboratories, then supplemented with recent studies. We examine the statistical power of AMA endpoint analysis and assess whether historical control data (HCD) can assist evidence-based interpretation of the endpoints, with 52 studies from 7 different laboratories. HCD can be used to understand assay performance post validation. The analysis identifies some need for flexibility in the interpretation of the Test Guidelines' performance criteria, including latitude with analytical variability and statistical analysis of late-stage animals. Additionally, more guidance is suggested for feed regiments and the selection criteria for batches of animals to initiate the assay. Potential Guideline refinements that improve interpretation of the data and have potential to reduce the number of vertebrate animals used in the conduct of AMAs are identified and discussed.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"157 ","pages":"Article 105773"},"PeriodicalIF":3.0,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010607","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}

引用次数: 0

A Comprehensive Safety Assessment of Algae Protein from Picochlorum for Human Consumption. 人类食用Picochlorum藻类蛋白的安全性综合评价。

IF 3 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2024-11-28 DOI: 10.1016/j.yrtph.2024.105753

Tomal Dattaroy, Manish R Shukla

{"title":"A Comprehensive Safety Assessment of Algae Protein from Picochlorum for Human Consumption.","authors":"Tomal Dattaroy, Manish R Shukla","doi":"10.1016/j.yrtph.2024.105753","DOIUrl":"https://doi.org/10.1016/j.yrtph.2024.105753","url":null,"abstract":"<p><p>The current trend happens to be that consumers are seeking nourishing, high quality sustainable protein sources to meet their nutritional needs, thus establishing a clear intent to broaden their protein horizon. Microalgae protein holds great promise in becoming the next vegan protein option. In the present study, protein extracted from the microalga Picochlorum maculatum has been thoroughly evaluated for its safety for human consumption through a battery of in-vivo and in-vitro tests. Bacterial reverse mutation assay indicates that the test substance is non-mutagenic and studies comprising of in-vitro chromosomal aberration test and the in-vivo mammalian micronucleus test showed that the test item is non-clastogenic, and therefore, lacks genotoxicity. Based the results of an acute oral toxicity study, the test item can be classified as \"Category 5\" as designated in a globally harmonized system for classification of chemicals. Further, 28-day and 90-day repeated dose oral toxicity studies did not result in any mortality or morbidity throughout the experimental period; none of the animal groups used in the study showed any abnormal clinical signs, establishing a \"No Observed Adverse Effect Level\" of Algae Protein Powder at 3000 mg kg bw<sup>-1</sup>. Moreover, the test item exhibited a positive impact on growth in test animals. Computational studies established extremely low allergenic potential of the test item.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"105753"},"PeriodicalIF":3.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771745","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