Regulatory Toxicology and Pharmacology最新文献_第7页

Retraction notice to “Repeated dose 28-day oral toxicity study of DEAE-Dextran in mice: An advancement in safety chemotherapeutics” [Regul. Toxicol. Pharm. 88 (2017) 262–272] 对“deae -葡聚糖小鼠28天重复剂量口服毒性研究：安全化疗药物的进展”的撤回通知[Regul]。Toxicol。医药杂志，88(2017):262-272。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-11-04 DOI: 10.1016/j.yrtph.2025.105982

引用次数: 0

Development of a digital tool for semi-quantitative assessment of pesticide exposure risk in greenhouses 开发用于温室农药暴露风险半定量评估的数字工具。

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.2025.105975

Pablo Fernández del Olmo, Julián Sánchez-Hermosilla, Ángel Callejón-Ferre, Marta Gómez-Galán, José Pérez-Alonso

{"title":"Development of a digital tool for semi-quantitative assessment of pesticide exposure risk in greenhouses","authors":"Pablo Fernández del Olmo, Julián Sánchez-Hermosilla, Ángel Callejón-Ferre, Marta Gómez-Galán, José Pérez-Alonso","doi":"10.1016/j.yrtph.2025.105975","DOIUrl":"10.1016/j.yrtph.2025.105975","url":null,"abstract":"<div><div>Accurate assessment of occupational exposure to plant protection products in greenhouses poses specific challenges due to confined environments, operator variability, and the limited suitability of existing models under real working conditions. This study presents the development of a digital tool that implements a semi-quantitative model for evaluating pesticide exposure risk among greenhouse workers. The model integrates task-specific variables across four exposure scenarios: mixing and loading, application, maintenance and re-entry; and applies a logarithmic scoring system to calculate an exposure index. This index is then combined with a toxicity score derived from product hazard classifications to obtain a comprehensive risk level, interpreted using a five-tier classification scheme with corresponding preventive recommendations. The application includes a preliminary questionnaire to ensure basic safety conditions are met and incorporates an automated update mechanism that maintains an up-to-date list of authorized products based on official registries. The tool was developed with a focus on usability and structured logic, supporting efficient data entry and interpretability of results. Field testing was carried out in different greenhouses under commercial production located in southeast Spain, confirming the coherence and functionality of the tool under practical conditions.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105975"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355878","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

Report on the European Partnership for Alternative Approaches to Animal Testing (EPAA) “New Approach Methodology (NAMs) User Forum”, 30–31 October 2024, Helsinki, Finland 欧洲动物试验替代方法伙伴关系报告（EPAA）“新方法方法论（NAMs）用户论坛”，2024年10月30日至31日，芬兰赫尔辛基

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-24 DOI: 10.1016/j.yrtph.2025.105980

Mark T.D. Cronin , Sophie Cable , Christian Desaintes , Sylvia E. Escher , Ellen Hessel , Ellen Fritsche , Petra Kern , Gavin Maxwell , Gladys Ouedraogo , Tomasz Sobanski , Matthias Wehr , Andrew White

{"title":"Report on the European Partnership for Alternative Approaches to Animal Testing (EPAA) “New Approach Methodology (NAMs) User Forum”, 30–31 October 2024, Helsinki, Finland","authors":"Mark T.D. Cronin , Sophie Cable , Christian Desaintes , Sylvia E. Escher , Ellen Hessel , Ellen Fritsche , Petra Kern , Gavin Maxwell , Gladys Ouedraogo , Tomasz Sobanski , Matthias Wehr , Andrew White","doi":"10.1016/j.yrtph.2025.105980","DOIUrl":"10.1016/j.yrtph.2025.105980","url":null,"abstract":"<div><div>The European Partnership for Alternative Approaches to Animal Testing (EPAA) held the “New Approach Methodology (NAMs) User Forum” at the European Chemicals Agency, Helsinki, Finland on 30–October 31, 2024. The User Forum brought together stakeholders from regulatory agencies, industry, non-governmental organisations (NGOs) and academia, as well as European Union competent authorities. Lessons learned from applying NAMs for regulatory use were provided by the European Food Safety Authority (EFSA) and European Chemicals Agency (ECHA). Progress in the development of the developmental and neurotoxicity <em>in vitro</em> battery (DNT IVB) and Alternative Safety Profiling Algorithm (ASPA) were described, as well as five case studies describing uses of NAMs for chemical safety assessment. The presentations confirmed progress in NAMs and, in particular, the value of tiered testing strategies to bring together different lines of evidence. Specifically, tiered testing strategies for non-animal information are organised into three tiers, which may be relevant to hazard, exposure and toxicokinetic information. Progress into, and the needs for improvement of, the tiered strategies were discussed with a particular focus on the types of NAMs (<em>in silico</em> and <em>in vitro</em>) that may be required at each tier and the how confidence may be assigned to making a decision.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105980"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145424548","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

Exploration of a framework to identify cohort of concern substances in medical device risk assessment 医疗器械风险评估中确定关注物质队列的框架探索。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-22 DOI: 10.1016/j.yrtph.2025.105976

Mao-wen Weng, Xiaoling (Sharlene) Dai, Shaoping Wu, Jared Wilsey, Matt Lewis, Robert F. Shulfer, Marika Kamberi

{"title":"Exploration of a framework to identify cohort of concern substances in medical device risk assessment","authors":"Mao-wen Weng, Xiaoling (Sharlene) Dai, Shaoping Wu, Jared Wilsey, Matt Lewis, Robert F. Shulfer, Marika Kamberi","doi":"10.1016/j.yrtph.2025.105976","DOIUrl":"10.1016/j.yrtph.2025.105976","url":null,"abstract":"<div><div>Cohort of concern substances (CoCs) present challenges in medical device toxicological risk assessment. They are excluded from the lifetime threshold of toxicological concern (TTC) per ISO/TS 21726, because their toxic dose is < 1.5 μg/day and they may present a higher cancer risk. Relying solely on structural similarities with known toxicants is inadequate for assessing carcinogenic potency. This study selected chemicals from the Carcinogenic Potency Database (CPDB) to establish a framework for identifying potential CoCs. To do that, a threshold of Cancer Risk Specific Dose (CRSD) < 0.025 μg/kg/day was initially applied. Chemicals meeting this criterion are recognized as CoCs. However, the risk assessment could be impeded by particular uncertainties, such as the inability to determine the CRSD. In such cases, the identified CoCs were further categorized based on their mutagenicity determined by the Ames test results. A scatterplot reveals a significant correlation between the carcinogenic potency [ Log(0.5/TD<sub>50</sub>)+7] and acute systemic toxicity [Log(LD<sub>50</sub>)] in the CoCs-Ames (−) group (R<sup>2</sup> = 0.72). For the CoCs-Ames (+) group (n = 124), 18 CoCs with available mutation slope data show cancer risk greater than the default risk of 1 in 100,000. This study provides a framework integrating scientific evidence and regulatory guidelines to identify potential CoCs.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105976"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368588","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 skin sensitization prediction model: an algorithm for real-world prediction of skin sensitization risk and minimization of human sensitization testing 皮肤致敏预测模型：一种用于真实世界皮肤致敏风险预测和人类致敏试验最小化的算法。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-09-13 DOI: 10.1016/j.yrtph.2025.105941

Ladan Fakhrzadeh , Otto Mills , Jim Bowman , Michael J. Cork , Alain Khaiat , James A. McGuire , Teginder Singh , Evren Atillasoy

{"title":"The skin sensitization prediction model: an algorithm for real-world prediction of skin sensitization risk and minimization of human sensitization testing","authors":"Ladan Fakhrzadeh , Otto Mills , Jim Bowman , Michael J. Cork , Alain Khaiat , James A. McGuire , Teginder Singh , Evren Atillasoy","doi":"10.1016/j.yrtph.2025.105941","DOIUrl":"10.1016/j.yrtph.2025.105941","url":null,"abstract":"<div><div>Skin sensitization testing to ensure the safety of skincare products for public consumption has largely relied on human repeat insult patch test (HRIPT). The desire to minimize reliance on HRIPT has prompted a search for alternative methods to assess the sensitization risk of consumer products to inform decision-making about their suitability before being brought to market. The novel Skin Sensitization Prediction Model (SSPM) is a methodology that draws upon a database consisting of more than 20 years of historical HRIPT data pertaining to 1274 unique product formulations, comprising 1226 common ingredients, for which HRIPT testing has been performed on 203,640 human subjects. The SSPM sets modifiable thresholds for each individual ingredient of a proposed formulation and for the formulation as a whole, applying risk calculations based on dosage density, potential for skin occlusion, potential for skin barrier impairment, and potential effects on immune-primed skin. Tabulations of a formulation's risk characteristics allow for a numerical risk calculation that is compared to the preset thresholds to determine whether the product may continue its development or should be reformulated or discontinued. This methodology points to a new model for sensitization testing for a wide array of products without recourse to <em>in vivo</em> testing.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105941"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070369","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

Suitability of the use of the intraperitoneal route in the in vivo micronucleus test to evaluate the genotoxicity of hair dyes 用腹膜内途径进行体内微核试验评价染发剂遗传毒性的适宜性

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-09-24 DOI: 10.1016/j.yrtph.2025.105948

Nicola J. Hewitt , Hind Assaf Vandecasteele , Paul Benndorf , Rolf Fautz , Anne Fuchs , Karma Fussell , Carsten Goebel , Torben König , Fabrice Nesslany , Juliane Werner , Paul Fowler

{"title":"Suitability of the use of the intraperitoneal route in the in vivo micronucleus test to evaluate the genotoxicity of hair dyes","authors":"Nicola J. Hewitt , Hind Assaf Vandecasteele , Paul Benndorf , Rolf Fautz , Anne Fuchs , Karma Fussell , Carsten Goebel , Torben König , Fabrice Nesslany , Juliane Werner , Paul Fowler","doi":"10.1016/j.yrtph.2025.105948","DOIUrl":"10.1016/j.yrtph.2025.105948","url":null,"abstract":"<div><div>New <em>in vivo</em> data cannot be generated for cosmetics. New safety assessments for genotoxicity must rely on <em>in vivo</em> data from the <em>in vivo</em> Mammalian Erythrocyte Micronucleus (MN) Test generated before the ban. Many used intraperitoneal (i.p.) administration, which is no longer recommended without scientific justification. Therefore, we investigated whether these studies are still valid for evaluating genotoxicity of hair dyes. Small to medium size molecules, including hair dyes, are preferentially absorbed via the portal vein and undergo first-pass metabolism, whereas large molecules are taken up by the lymphatics directly into the systemic circulation. Plasma concentrations of small molecules are generally similar, if not higher, after i.p. than after p.o. administration. Importantly, outcomes from <em>in vivo</em> MN Test using the i.p. and p.o. routes were equivalent. Most genotoxic carcinogens with positive outcomes in the <em>in vivo</em> MN Test were administered by i.p. injection. Differences between <em>in vivo</em> genotoxicity assay results using administration routes are attributed to the Mode of Action and/or tissue-specific effects. In conclusion, the i.p. route achieves sufficiently high internal exposure i.e., in the plasma and bone marrow. Therefore, legacy OECD test guideline compliant studies using the i.p. route are valid for current safety assessments of hair dyes.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105948"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145160017","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

Comparative assessment of 24 pigment dusts reveals analogue inhalation effects 24种颜料粉尘的比较评估揭示了类似的吸入效应。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-09-11 DOI: 10.1016/j.yrtph.2025.105934

Anne Herrmann , Laura Puente , Lan Ma-Hock , Heidi Stratmann

{"title":"Comparative assessment of 24 pigment dusts reveals analogue inhalation effects","authors":"Anne Herrmann , Laura Puente , Lan Ma-Hock , Heidi Stratmann","doi":"10.1016/j.yrtph.2025.105934","DOIUrl":"10.1016/j.yrtph.2025.105934","url":null,"abstract":"<div><div>A comparative analysis of 24 short-term inhalation studies with pigments revealed that while all pigments were well-tolerated without signs of systemic toxicity, most caused pulmonary inflammation and a slight to moderate increase in lung weight and neutrophil infiltration. The pathological and histopathological effects and changes observed were reversible at low and mid-level concentrations and declined within the 21 days recovery at the maximum concentration of 60 mg/m<sup>3</sup>. The slight to moderate epithelial hypertrophy and hyperplasia of the airways is considered being non-specific and adaptive. Benchmark calculations showed a 10 % lung weight increase and neutrophil infiltration at 5–20 mg/m<sup>3</sup>. Exposure levels above 30 mg/m<sup>3</sup> ended up in lung overload and impaired alveolar macrophage mediated lung clearance. Pigment particles showed a consistent effect pattern of particle-related pulmonary inflammation after short-term exposure, which was transient in nature below lung overload causing concentrations. Sub-chronic inhalation studies for three of the pigments tested confirmed the identified effect-pattern and the absence of substance-specific or chemical class-related effects. Consequently, classification and labelling according to the regulatory guidance values and criteria in place is not considered meaningful. The establishment of clear definitions, criteria and human exposure limits for poorly soluble particles is considered a pragmatic approach.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105934"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058519","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

Safety and regulatory assessment of heat-killed Lactiplantibacillus plantarum strain L-137 (HK L-137) as a food ingredient 热杀植物乳杆菌L-137 （HK L-137）作为食品原料的安全性和监管评价。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-22 DOI: 10.1016/j.yrtph.2025.105977

Ashley Roberts , Hiroaki Sato , Masahiko lino , Toshimitsu Kuribayashi

{"title":"Safety and regulatory assessment of heat-killed Lactiplantibacillus plantarum strain L-137 (HK L-137) as a food ingredient","authors":"Ashley Roberts , Hiroaki Sato , Masahiko lino , Toshimitsu Kuribayashi","doi":"10.1016/j.yrtph.2025.105977","DOIUrl":"10.1016/j.yrtph.2025.105977","url":null,"abstract":"<div><div>The safety of heat-killed <em>Lactiplantibacillus plantarum</em> strain L-137 (HK L-137) was evaluated in a 28-day dose range finding study and a 90-day study in Crl:CD (SD) rats administered a formulation containing 20 % HK L-137 and 80 % dextrin (LP20) at dose levels of 0, 1,000, 2000 and 3000 mg/kg bw/day by gavage. No death or moribundity occurred in any animal in any group and no effects were reported in terms of bodyweight gain or food consumption at each of the dose levels. In the 90-day study, no treatment-related adverse effects were recorded in each dose group for the functional observation battery, spontaneous activity movement or ophthalmological measurements, hematology, clinical chemistry, thyroid stimulating hormone, triiodothyronine, urinalysis, vaginal smears, gross pathology, organ weights or histopathology. While several statistically significant changes were identified including male thyroxine levels, these were shown not to be dose-dependent, were of low magnitude, with the majority of changes found to be within historical control values. As there were no histological correlates, these changes were considered incidental without toxicologic significance and not attributable to HK L-137. The NOEL for LP20 in the 90-day toxicity study was therefore considered 3000 mg/kg bw/day or 600 mg/kg bw/day for HK L-137 in both males and females for food use.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105977"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145368621","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

Impurity qualification requirements for drug-linkers related impurities used to generate antibody-drug conjugates 用于产生抗体-药物偶联物的药物连接物相关杂质的杂质鉴定要求。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-23 DOI: 10.1016/j.yrtph.2025.105974

Osama Chahrour , Paul D. Cornwell , Penny Leavitt , Elizabeth A. Martin , Christina de Zafra , Susanne Glowienke , Angela White , Andrew Teasdale , Bruce Trela , Mayur S. Mitra , Wolfgang Muster , Jim Harvey

{"title":"Impurity qualification requirements for drug-linkers related impurities used to generate antibody-drug conjugates","authors":"Osama Chahrour , Paul D. Cornwell , Penny Leavitt , Elizabeth A. Martin , Christina de Zafra , Susanne Glowienke , Angela White , Andrew Teasdale , Bruce Trela , Mayur S. Mitra , Wolfgang Muster , Jim Harvey","doi":"10.1016/j.yrtph.2025.105974","DOIUrl":"10.1016/j.yrtph.2025.105974","url":null,"abstract":"<div><div>This position paper presents a science-based, holistic assessment of the toxicological risks posed by organic impurities in drug-linkers (D-L) used as intermediates in the production of Antibody-Drug Conjugates (ADCs) for oncology indications. The analysis outlined in this manuscript demonstrates that organic impurities present at levels at or below 1.0 % w/w in D-L intermediates are unlikely to result in adverse toxicological effects upon administration of the final ADC drug product. Due to the extremely low exposure (molar and weight) associated with 1.0 % w/w impurity level in the D-Ls, the authors propose to maintain the ICH Q3A criteria of not more than 1 mg/day limit however increase the qualification limit criteria for D-L related impurities from 0.15 % to 1.0 % w/w. Additionally, a methodology is introduced to assess the level of concern for non-conjugatable organic impurities, utilizing process-specific and ADC-specific factors to justify specifications for these impurities in D-L intermediates. Based on the minimal risk associated with D-L impurities at or below the discussed levels, the paper proposes a workflow for quality risk management of such impurities in D-Ls.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105974"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370444","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

Quantitative next generation risk assessment for skin sensitization - application of regression models based on in vitro data to estimate point of departure 定量下一代皮肤致敏风险评估-应用基于体外数据的回归模型来估计起点。

IF 3.5 4区医学

Regulatory Toxicology and Pharmacology Pub Date : 2026-01-01 Epub Date: 2025-10-14 DOI: 10.1016/j.yrtph.2025.105964

Isabelle Lee , Mihwa Na , Maura Lavelle , Isabella Schember , Marissa A. Guttenberg , G Frank Gerberick , Andreas Natsch , Cindy Ryan , Anne Marie Api

{"title":"Quantitative next generation risk assessment for skin sensitization - application of regression models based on in vitro data to estimate point of departure","authors":"Isabelle Lee , Mihwa Na , Maura Lavelle , Isabella Schember , Marissa A. Guttenberg , G Frank Gerberick , Andreas Natsch , Cindy Ryan , Anne Marie Api","doi":"10.1016/j.yrtph.2025.105964","DOIUrl":"10.1016/j.yrtph.2025.105964","url":null,"abstract":"<div><div>Quantitative risk assessment (QRA) for dermal sensitization is essential for determining safe concentrations of skin sensitizers in consumer products. The fragrance industry developed the QRA2 approach, which uses the No Expected Sensitization Induction Level (NESIL) as a starting reference dose or point of departure (PoD). Animal alternatives for potency assessment have emerged to calculate quantitative PoDs. One such alternative is <em>in vitro</em>-based regression models.</div><div>Herein, a framework for incorporating regression models into next-generation risk assessment (NGRA) is presented. The framework begins with hazard assessment using <em>in vitro</em> methods (OECD Guideline 497), followed by PoD calculation through regression models, and completed with QRA2. After determining a PoD, uncertainty factors may be considered to derive a new approach methodology NESIL (NAM-NESIL). Case studies are presented with two sensitizers, <em>p</em>-mentha-1,8-dien-7-al (CAS # 2111-75-3) and 3-propylidenephthalide (CAS # 17369-59-4), calculating acceptable exposure levels (AELs) for products like deodorants and bar soaps. Ratios of the AELs to consumer exposure levels (CELs) were then calculated to determine whether the current use is safe. Comparison of QRA based on NAM-NESILs to historically human-derived NESILs supports the reliability of <em>in vitro</em> models. This approach offers a promising alternative for PoD derivation, potentially eliminating the dependence on in-vivo data.</div></div>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":"164 ","pages":"Article 105964"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308926","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