Regulatory Toxicology and Pharmacology最新文献_第9页

Chemical characterization and toxicological evaluation of acrylic-based dental implant devices used for different purposes within the scope of ISO 10993 ISO 10993范围内用于不同用途的丙烯酸基牙科植入装置的化学特性和毒理学评价。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-09-27 DOI: 10.1016/j.yrtph.2025.105949

Tuğçe Kuruca , Deniz Demir , Esin Akarsu , Murat Akarsu

Medical devices have the potential to release chemical constituents, either as residual manufacturing additives or as leachable under clinical conditions, which may pose potential toxicological risks. Therefore, comprehensive chemical characterization is crucial to identify and quantify extractable compounds that could migrate from the device during clinical use, in accordance with ISO 10993 standards.

This study provides a comprehensive chemical characterization and toxicological risk assessment of acrylic-based dental devices intended for various clinical applications. By adhering to ISO 10993–12:2021 for extraction protocols and employing both polar (water) and apolar (50:50 ethanol-water) solvents, leachable were analyzed after 72-h incubations at 50 °C. Fourier Transform Infrared Spectroscopy (FTIR) confirmed the use of polymethyl methacrylate (PMMA) in device matrices, while thermogravimetric analysis (TGA) revealed the presence of inorganic pigments.

Extractable compounds were identified by using a broad range of analytical techniques-including Gas Chromatography-Mass Spectrometry (GC-MS), High Performance Liquid Chromatography (HPLC), UV–VIS–NIR Spectrophotometry because of extractable studies, Liquid Chromatography – Tandem Mass Spectrometry (LC-MS/MS) and Inductively Coupled Plasma–Optical Emission Spectrometry (ICP-OES) techniques, detecting compounds such as phenyl benzoate, N,N-dimethyl-p-toluidine, benzoyl peroxide, ethylene glycol dimethacrylate, and benzoic acid. Toxicological risk assessments were subsequently conducted in accordance with ISO 10993–17:2023, demonstrating that all tested devices were biocompatible and posed no toxicological hazard under intended clinical conditions.

医疗器械有可能释放化学成分，作为残留的制造添加剂或在临床条件下可浸出，这可能构成潜在的毒理学风险。因此，根据ISO 10993标准，全面的化学表征对于识别和量化临床使用期间可能从设备迁移的可提取化合物至关重要。本研究提供了用于各种临床应用的丙烯酸基牙科器械的综合化学特性和毒理学风险评估。通过遵循ISO 10993- 12:21 21提取方案，并采用极性（水）和极性（50:50乙醇-水）溶剂，在50°C下培养72小时后分析可浸出性。傅里叶变换红外光谱（FTIR）证实了在器件基质中使用了聚甲基丙烯酸甲酯（PMMA），而热重分析（TGA）显示了无机颜料的存在。可提取化合物通过广泛的分析技术进行鉴定，包括气相色谱-质谱（GC-MS），高效液相色谱（HPLC），紫外-可见-近红外分光光度法（因为可提取研究），液相色谱-质谱（LC-MS/MS）和电感耦合等离子体质谱（ICP-OES）技术，检测化合物如苯甲酸苯酯，N，N-二甲基-对甲苯胺，过氧化苯甲酰，乙二醇二甲基丙烯酸酯，还有苯甲酸。随后根据ISO 10993-17:2023进行毒理学风险评估，证明所有测试设备具有生物相容性，并且在预期的临床条件下不构成毒理学危害。

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引用次数: 0

Expert panel evaluation of the tumor modes of action for 1,4-dioxane and their implications for human risk assessment 专家小组对1,4-二恶烷的肿瘤作用方式及其对人类风险评估的影响的评估。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-09-25 DOI: 10.1016/j.yrtph.2025.105950

C.R. Kirman , J.S. Bus , S. Gupta , J.E. Klaunig , M.E. Meek , S.M. Hays

Mode of action (MOA) plays an important role in key decisions made in risk assessments, including that for low-dose extrapolation. To support MOA-dependent decisions for 1,4-dioxane (1,4-DX), an independent panel of topic experts evaluated the available evidence on the MOA and human relevance of 1,4-DX tumors reported in rodent studies. The panel considered MOA data on liver tumors in rodents, as well as for other tissue sites (nasal cavity, peritoneal mesothelioma). For liver tumors, the panelists found strongest support for an indirect genotoxic MOA involving metabolic saturation of the enzyme that metabolizes 1,4-DX (CYP2E1), followed by induction of CYP2E1, oxidative stress, cytotoxicity, and regenerative proliferation. Metabolic saturation was identified as an early key event. Although available evidence for nasal and peritoneal tumors was limited, similar non-genotoxic MOAs were considered plausible. For all three tumor types, confidence ratings (scale of −5 to +5) from the panel for the best supported MOAs (+2.5 to +3.3) were significantly higher than the confidence rating for a direct genotoxic MOA (−3.8 to −4.5). The conclusions from this independent panel, which included careful consideration of recently published studies, provide support for use of non-linear extrapolation methods in human health risk assessment for 1,4-DX rodent tumors.

作用方式（MOA）在风险评估（包括低剂量外推）的关键决策中发挥着重要作用。为了支持对1,4-二恶烷（1,4- dx）依赖于MOA的决定，一个独立的专题专家小组评估了啮齿动物研究中报道的关于MOA和1,4- dx肿瘤与人类相关性的现有证据。专家组考虑了啮齿类动物肝脏肿瘤以及其他组织部位（鼻腔、腹膜间皮瘤）的MOA数据。对于肝脏肿瘤，小组成员发现间接基因毒性MOA最有力的支持，涉及代谢1,4- dx （CYP2E1）的酶的代谢饱和，随后是CYP2E1的诱导、氧化应激、细胞毒性和再生增殖。代谢饱和被确定为早期关键事件。虽然鼻肿瘤和腹膜肿瘤的证据有限，但类似的非基因毒性moa被认为是合理的。对于所有三种肿瘤类型，来自小组的最佳支持MOA（+2.5至+3.3）的置信度评分（-5至+5）明显高于直接基因毒性MOA（-3.8至-4.5）的置信度评分。该独立小组的结论包括仔细考虑最近发表的研究，为在1,4- dx啮齿动物肿瘤的人类健康风险评估中使用非线性外推法提供了支持。

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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 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub 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

New in vivo data cannot be generated for cosmetics. New safety assessments for genotoxicity must rely on in vivo data from the in vivo 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 in vivo MN Test using the i.p. and p.o. routes were equivalent. Most genotoxic carcinogens with positive outcomes in the in vivo MN Test were administered by i.p. injection. Differences between in vivo 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.

化妆品不能产生新的体内数据。新的遗传毒性安全评估必须依赖于禁令颁布前的哺乳动物红细胞微核（MN）试验的体内数据。许多人使用腹腔（i.p）给药，没有科学依据不再推荐。因此，我们调查了这些研究是否仍然有效，以评估染发剂的遗传毒性。小到中等大小的分子，包括染发剂，优先通过门静脉吸收并进行第一次代谢，而大分子则由淋巴管直接进入体循环。服药后小分子血药浓度通常与服药后相似，甚至更高。重要的是，使用ip和po途径进行体内MN测试的结果是相同的。大多数遗传毒性致癌物在体内MN试验中呈阳性结果，通过i.p.注射给药。不同给药途径的体内遗传毒性测定结果的差异归因于作用方式和/或组织特异性效应。总之，ip途径达到足够高的内部暴露，即血浆和骨髓。因此，使用ip路线的传统OECD测试指南符合研究对当前染发剂的安全性评估是有效的。

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引用次数: 0

Beyond molecular structure: Comparing Australian and European regulatory approaches to nano-identification and classification 超越分子结构：比较澳大利亚和欧洲的纳米鉴定和分类管理方法

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-09-24 DOI: 10.1016/j.yrtph.2025.105947

Sarah Wilson, Stephen Northey, Rachael Wakefield-Rann, Nick Florin

Across regulation and toxicology, nanomaterials challenge foundational assumptions about substance identity and risk assessment. Through comparing substance identification requirements across Australian and European industrial chemical regulation – the Australian Industrial Chemicals Introduction Scheme (AICIS) and the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) respectively – this article explores how legal actors have incorporated the evolving science of nanotoxicology into the identification frameworks that establish regulatory approaches. These frameworks are important as they structure how regulators delineate between ‘new’ substances requiring novel risk assessment and regulatory approval, and ‘existing’ substances that have already been assessed.

The findings reveal REACH and AICIS have created contrasting approaches to nano-identification. REACH employs a comprehensive multifactorial method aligned with emerging nanotoxicological principles, while AICIS relies on broader structure-based CAS identifiers. These frameworks differ in both factors used and the specificity of material identification. Such regulatory data discrepancies could impact nano-risk regulation, creating potential scientific and legal vulnerabilities for managing distinct nanoforms with variable risk identities in Australia's regulatory environment. This analysis shows that the effective regulation of complex materials depends not just on accurate material characterisation, but on the structural design of legal information systems that mediate between scientific knowledge and regulatory action.

在监管和毒理学方面，纳米材料挑战了关于物质识别和风险评估的基本假设。通过比较澳大利亚和欧洲工业化学品法规的物质识别要求——澳大利亚工业化学品引入计划（AICIS）和化学品的注册、评估、授权和限制（REACH）——本文探讨了法律行为者如何将纳米毒理学的发展科学纳入建立监管方法的识别框架。这些框架很重要，因为它们构建了监管机构如何区分需要新的风险评估和监管批准的“新”物质和已经评估的“现有”物质。研究结果表明，REACH和AICIS创造了不同的纳米鉴定方法。REACH采用了一种综合的多因素方法，与新兴的纳米毒理学原理相一致，而AICIS依赖于更广泛的基于结构的CAS标识符。这些框架在使用的因素和材料识别的特异性方面有所不同。这种监管数据差异可能会影响纳米风险监管，在澳大利亚的监管环境中，为管理具有可变风险特征的不同纳米形式造成潜在的科学和法律漏洞。这一分析表明，对复杂材料的有效监管不仅取决于准确的材料特征，还取决于在科学知识和监管行动之间进行调解的法律信息系统的结构设计。

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引用次数: 0

How many mutagens are missed under REACH due to limited low tonnage information requirements? 由于有限的低吨位信息要求，在REACH下遗漏了多少诱变剂？

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-09-22 DOI: 10.1016/j.yrtph.2025.105946

Rune Hjorth , Joop de Knecht , Eva B. Wedebye , Nikolai G. Nikolov , Damiën van Berlo , Henrik Tyle

For industrial substances registered under REACH at 1–10 tonnes per registrant/year, only the Ames test is required to address mutagenicity. When a substance tests positive in the Ames test, further testing is needed, but when the test result is negative, additional mutagenicity testing is only mandatory at a higher tonnage level. It is correspondingly known that some mutagens produced up to 10 tonnes per year/registrant are not identified. Based on battery (Q)SAR modelling, relying on agreement from both in vitro and in vivo models, advisory self-classifications (ASC) for mutagenicity are offered by the Danish EPA. In this present study, substances with ASC for mutagenicity are compared to the identified mutagens in low tonnage REACH registrations. We conclude that for only about a quarter of the low-tonnage substances with an Muta. 2 ASC, a positive experimental Ames result is available, leading to follow-up under REACH. We recommend improving the identification of mutagenic substances at the 1–10 tonnage band by including the in vitro micronucleus test to supplement the Ames test. Concerningly, the few low tonnage REACH dossiers that do provide in vivo data, mostly report negative micronucleus test results that are not conclusive due to missing information on bone marrow exposure.

对于在REACH下注册的工业物质，每个注册人/年1-10吨，只需Ames测试即可解决致突变性问题。当一种物质在Ames测试中呈阳性时，需要进一步测试，但当测试结果为阴性时，仅在更高吨位水平上强制进行额外的诱变性测试。相应地，我们知道有些诱变剂的年产量为10吨/注册人，但没有加以确定。基于电池(Q)SAR模型，依赖于体外和体内模型的一致性，丹麦环保局提供了致突变性的咨询自我分类（ASC）。在本研究中，将具有ASC致突变性的物质与低吨位REACH注册中已确定的致突变性物质进行比较。我们得出的结论是，只有大约四分之一的低吨位物质具有Muta. 2 ASC，可获得积极的实验Ames结果，从而导致REACH下的后续工作。我们建议通过增加体外微核试验来补充Ames试验，以改进1-10吨位波段致突变物质的鉴定。值得关注的是，少数低吨位的REACH档案确实提供了体内数据，但大多报告了阴性的微核试验结果，由于缺少关于骨髓暴露的信息，这些结果不是结论性的。

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引用次数: 0

WITHDRAWN: Analysis and Comparison of New Psychoactive Substances (NPS) Regulation in Mainland China, Taiwan, Hong Kong, and Macao: Lessons for Global Control 中国大陆、台湾、香港和澳门新精神活性物质（NPS）法规的分析与比较：全球管制的经验教训。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-09-15 DOI: 10.1016/j.yrtph.2025.105943

Zhigang Zhou, Lanjun Zheng

This article has been withdrawn at the request of the author(s) and/or editor due to an error in the publishing process. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies-and-standards/article-withdrawal

本研究分析了中国大陆、台湾、香港和澳门的新精神活性物质（NPS）监管情况，为全球NPS管制提供重要参考数据。该报告首次分析了中国的NPS立法、调度方法、调度更新和法律诉讼，并讨论了NPS监管的改进。发现个体清单与通用调度相结合是NPS调度的可行方法。台湾每三个月定期更新一次NPS排程，香港在通用排程中频繁更新化学母核及相关取代基，都是很有价值的做法。中国大陆对毒品的非刑事化意味着刑罚较轻，台湾对吸毒者进行的关于毒品危害的强制性教育也值得考虑。台湾和澳门对非营利性机构进行了分类，因为他们认为对不同类别的非营利性机构实施不同的处罚更为科学。建议国际社会采取个体清单与通用目录相结合的方式，定期更新NPS目录，持续更新NPS目录中的化学母核和相关取代基，对NPS进行分类和处罚，并对NPS使用者实施强制教育。

引用次数: 0

The association between cadmium exposure and the risk of early liver disease: A systematic review and meta-analysis 镉暴露与早期肝病风险之间的关系：一项系统综述和荟萃分析。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-09-15 DOI: 10.1016/j.yrtph.2025.105942

Hualing Zhang , Yue Jing , Lan Guan , Jianlan Luo , Ming Zeng

Currently, liver diseases are considered to be one of the most prevalent diseases that jeopardize people's health. Existing studies have found that heavy metal cadmium (Cadmium, Cd) exposure is associated with liver disease, but the results of studies on the risk of cadmium on liver disease are inconsistent. In order to further investigate the relationship between cadmium exposure and the risk of early liver disease in the population, this study was conducted by searching PubMed, Cochrane Library, Web of Science, CNKI and Wanfang databases and performing meta-analysis of the relevant literature, so as to systematically evaluate the effect of cadmium exposure on the risk of liver disease. A total of 5201 relevant articles were retrieved. Based on inclusion and exclusion criteria, 25 articles were included in the meta-analysis. Review Manager 5.4 was used for quality assessment, with most studies rated as low risk of bias. Heterogeneity testing showed significant results (P < 0.05). Meta-analysis showed that cadmium exposure increased the risk of elevated liver enzymes (OR = 1.38, 95 % CI: 1.27–1.50), MAFLD (OR = 1.14, 95 % CI: 1.07–1.22) and liver fibrosis (OR = 1.39, 95 % CI: 1.14–1.70). Sensitivity analysis and publication bias detection indicated that the results were reliable. Therefore, the conclusion of this study is that environmental cadmium exposure increases the risk of liver disease, and the extent and dose of cadmium exposure in the population should be further controlled.

目前，肝脏疾病被认为是危害人类健康的最普遍的疾病之一。已有研究发现重金属镉（cadmium, Cd）暴露与肝脏疾病有关，但有关镉对肝脏疾病风险的研究结果并不一致。为了进一步探讨镉暴露与人群早期肝病风险的关系，本研究通过检索PubMed、Cochrane Library、Web of Science、CNKI和万方等数据库，并对相关文献进行meta分析，系统评价镉暴露对人群早期肝病风险的影响。共检索到5201篇相关文章。根据纳入和排除标准，25篇文章被纳入meta分析。使用Review Manager 5.4进行质量评估，大多数研究被评为低偏倚风险。异质性检验结果有显著性差异（P < 0.05）。荟萃分析显示，镉暴露增加了肝酶升高（OR=1.38, 95% CI: 1.27-1.50）、MAFLD （OR=1.14, 95% CI: 1.07-1.22）和肝纤维化（OR=1.39, 95% CI: 1.14-1.70）的风险。敏感性分析和发表偏倚检测表明结果是可靠的。因此，本研究的结论是环境镉暴露会增加肝脏疾病的风险，人群中镉暴露的程度和剂量应进一步控制。

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引用次数: 0

Dose level selection for developmental and reproductive toxicology (DART) studies: Insights from the EUROTOX 2024 satellite workshop 发育和生殖毒理学（DART）研究的剂量水平选择：来自EUROTOX 2024卫星研讨会的见解。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-09-15 DOI: 10.1016/j.yrtph.2025.105945

Fiona Sewell , Mark Blee , Daphne Peperkamp-van den Oetelaar , Manon Beekhuijzen

In 2022, the European Chemicals Agency (ECHA) issued updated advice on high-dose selection for developmental and reproductive toxicity (DART) studies, aiming to ensure reproductive hazards are identified without causing excessive toxicity or severe suffering in test animals. However, the advice faced much criticism from the scientific community with concerns around animal welfare and use of unnecessarily high doses. To better understand the background to the advice and explore the implications of this guidance, a satellite workshop was held at EUROTOX 2024 in Copenhagen, in collaboration with ECHA, that brought together over 120 global stakeholders from industry, regulatory bodies, academia, and contract research organisations. Discussions focused on the interpretation and application of the advice across OECD test guidelines (TGs 414, 421/422, and 443), highlighting areas of uncertainty, such as dose spacing, sex-specific sensitivity, and balancing fertility versus developmental endpoints. Interactive sessions revealed differing interpretations and underscored the need for clearer guidance. The workshop fostered mutual understanding and identified opportunities to refine the advice to better align scientific, regulatory, and animal welfare objectives. This report summarises key discussions and outlines the need for continued collaboration to support harmonised, scientifically justified dose selection practices that support both human health protection and 3Rs principles

2022年，欧洲化学品管理局（ECHA）发布了关于发育和生殖毒性（DART）研究的高剂量选择的最新建议，旨在确保在确定生殖危害的同时，不会对试验动物造成过度毒性或严重痛苦。然而，这一建议遭到了科学界的批评，他们担心动物福利和不必要的高剂量使用。为了更好地了解该建议的背景并探索该指南的影响，与ECHA合作，在哥本哈根EUROTOX 2024举办了一个卫星研讨会，汇集了来自行业，监管机构，学术界和合同研究组织（cro）的120多个全球利益相关者。讨论的重点是经合组织测试指南（TGs 414、421/422和443）中建议的解释和应用，强调了不确定性领域，如剂量间隔、性别特异性敏感性和生育与发育终点的平衡。互动式会议揭示了不同的解释，并强调需要更明确的指导。研讨会促进了相互理解，并确定了改进建议的机会，以更好地协调科学、监管和动物福利目标。本报告总结了主要讨论并概述了继续合作的必要性，以支持既支持人类健康保护又支持3Rs原则的统一的、科学合理的剂量选择做法。

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引用次数: 0

An extended Reference Chemical Potency List (RCPL) for characterising the performance of New Approach Methodologies (NAMs) in measuring the skin sensitisation potency of fragrance chemicals 一种扩展的参考化学效价表（RCPL），用于表征新方法方法（NAMs）在测量芳香化学品的皮肤致敏效价方面的性能。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-09-13 DOI: 10.1016/j.yrtph.2025.105944

Amaia Irizar , Hans Bender , James W. Bridges , Peter Griem , Andreas Natsch , Matthias Vey , Ian Kimber

The development of a Reference Chemical Potency List (RCPL), and its purpose, has been described previously. That original RCPL comprised 33 chemicals, of varying skin sensitising activity, for each of which a discrete Potency Value (PV) was derived, based upon the best available human and/or animal (local lymph node assay) data. The purpose of the RCPL was to provide a reliable tool that would facilitate evaluation of the ability of New Approach Methodologies (NAMs) to measure skin sensitising potency. We here report the construction of an extended RCPL with 77 additional chemicals by applying the weight of evidence framework used previously. This extended RCPL adheres to the salient features of the original database. These comprise a focus largely on fragrance chemicals, provision of a wide range of chemical structures and of skin sensitising potency, the inclusion of both direct and indirect (pre- and pro-) haptens, the exclusion of NAMs data for the derivation of PVs, and avoidance of the use of potency categories for the classification of chemicals. It is anticipated that this extended RCPL will provide a more powerful database with which to assess the strengths and weakness of recently developed NAMs in the measurement of skin sensitising potency.

参考化学效价表（RCPL）的制定及其目的已在前面描述过。最初的RCPL包含33种化学物质，具有不同的皮肤致敏活性，每种化学物质的独立效价（PV）是基于最佳可用的人类和/或动物（局部淋巴结测定）数据得出的。RCPL的目的是提供一个可靠的工具，以促进评估新方法方法（NAMs）测量皮肤致敏效力的能力。我们在这里报告了一个扩展的RCPL的建设与77个额外的化学品应用权重的证据框架以前使用。这个扩展的RCPL遵循原始数据库的显著特性。这些包括主要关注芳香化学品，提供广泛的化学结构和皮肤致敏效力，包括直接和间接（前半抗原和前半抗原）半抗原，排除衍生pv的NAMs数据，以及避免使用效力类别对化学品进行分类。预计这种扩展的RCPL将提供一个更强大的数据库，用于评估最近开发的NAMs在测量皮肤致敏效力方面的优势和劣势。

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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 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub 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

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 in vivo testing.

为了确保公众消费护肤品的安全性，皮肤致敏试验在很大程度上依赖于人体重复损伤斑贴试验（HRIPT）。为了尽量减少对HRIPT的依赖，人们开始寻找其他方法来评估消费品的致敏风险，以便在将其推向市场之前就其适用性向决策部门提供信息。新的皮肤致敏预测模型（SSPM）是一种方法，它利用了一个数据库，该数据库由20多年的历史HRIPT数据组成，涉及1,274种独特的产品配方，包括1,226种常见成分，为此HRIPT测试已在203,640名人类受试者中进行。SSPM为建议配方的每个成分和整个配方设置可修改的阈值，应用基于剂量密度的风险计算，潜在的皮肤闭塞，潜在的皮肤屏障损伤，以及对免疫启动皮肤的潜在影响。配方的风险特征表允许进行数值风险计算，将其与预设阈值进行比较，以确定产品是否可以继续开发或应该重新配制或停产。这种方法指出了一种新的模型，用于广泛的产品敏化测试，而不依赖于体内测试。

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