Regulatory Toxicology and Pharmacology最新文献_第6页

Experiences and initiatives on pharmacokinetic modeling and simulation data analysis: Perspectives from the Brazilian Health Regulatory Agency (ANVISA) 药物动力学建模和模拟数据分析方面的经验和举措：巴西卫生监管局（ANVISA）的观点。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-22 DOI: 10.1016/j.yrtph.2024.105728

Luiza Novaes Borges , Eduardo Agostinho Freitas Fernandes , Érico Miroro de Oliveira , Victor Gomes Pereira , Andréa Diniz

The landscape of drug product development and regulatory sciences is evolving, driven by the increasing application of systems thinking and modeling and simulation (M&S) techniques, especially from a biopharmaceutics perspective. Patient-centric quality standards can be achieved within this context through the application of quality by design (QbD) principles and M&S, specifically by defining clinically relevant dissolution specifications (CRDS). To this end, it is essential to bridge in vitro results to drug product in vivo performance, emphasizing the need to explore the translational capacity of biopharmaceutics tools. Physiologically based M&S analyses offer a unique avenue for integrating the drug, drug product, and biological properties of a target organism to study their interactions on the pharmacokinetic response. Accordingly, Physiologically Based Biopharmaceutics Modeling (PBBM) has seen increasing use to support drug development and regulatory applications globally. In Brazil, a Model-Informed Drug Development (MIDD) policy and strategic project are not yet established, limiting applicability of M&S techniques. Drawing from the experience of the ANVISA-Academia PBBM Working Group (WG), this article assesses the opportunities and challenges for pharmacometrics (PMx) in Brazil and proposes strategies to advance the adoption of M&S analyses into regulatory decision-making.

在越来越多地应用系统思维和建模与模拟（M&S）技术的推动下，药物产品开发和监管科学的格局正在发生变化，尤其是从生物制药的角度来看。在此背景下，可以通过应用质量设计（QbD）原则和 M&S，特别是通过定义临床相关溶出度规范（CRDS），实现以患者为中心的质量标准。为此，必须将体外结果与药物产品的体内性能联系起来，这强调了探索生物制药工具转化能力的必要性。基于生理学的 M&S 分析为整合药物、药物产品和目标生物体的生物特性提供了一条独特的途径，以研究它们在药代动力学反应中的相互作用。因此，基于生理学的生物药剂学建模（PBBM）在全球范围内被越来越多地用于支持药物开发和监管应用。在巴西，模型信息药物开发（MIDD）政策和战略项目尚未建立，限制了 M&S 技术的适用性。本文借鉴巴西国家药品管理局-学术界 PBBM 工作组（WG）的经验，评估了巴西药物计量学（PMx）面临的机遇和挑战，并提出了推动在监管决策中采用 M&S 分析的策略。

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引用次数: 0

Data collection initiatives of the crop protection industry – A mission to improve non-dietary risk assessment in Europe 作物保护行业的数据收集倡议--改善欧洲非饮食风险评估的使命。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-20 DOI: 10.1016/j.yrtph.2024.105727

Neil Morgan , Sarah Adham , Edgars Felkers , Felix M. Kluxen , Christian J. Kuster , Christiane Wiemann

Plant protection products (PPPs) undergo rigorous safety assessments. In Europe, non-dietary risk assessments for operators, workers, bystanders and residents are highly conservative as this area of exposure science has historically been data poor. CropLife Europe (CLE) companies have collaborated to generate new data and pool existing data to refine the approaches prescribed by the European Food Safety Authority (EFSA) guidance on non-dietary exposure (2022).

This article summarises key activities, beginning with the development of the Agricultural Operator Exposure Model (AOEM) and covers projects which refine current approaches to bystander, resident and re-entry worker assessment, including the Bystander Resident Orchards Vineyards (BROV) project, improvements to the Bystander and Resident Exposure Assessment Model for spray drift (BREAM), proposals for refined vapour inhalation assessments, and a meta-analysis of Dislodgeable Foliar Residue (DFR) data. A study quantifying the benefits of using closed transfer systems, an appraisal of the inherent compounded conservatism in current risk assessment paradigms and the development of a new seed treatment model by the SeedTROPEX taskforce are also introduced.

These industry-led activities underscore the critical role of non-dietary exposure in the registration process for PPPs and reflect an ongoing commitment to provide farmers with effective crop protection solutions while ensuring safety.

植物保护产品（PPPs）需要经过严格的安全评估。在欧洲，针对操作人员、工人、旁观者和居民的非饮食风险评估非常保守，因为这一领域的暴露科学历来数据贫乏。欧洲作物生命协会（CLE）旗下各公司已开展合作，生成新数据并汇集现有数据，以完善欧洲食品安全局（EFSA）非饮食暴露指南（2022 年）规定的方法。本文总结了从开发农业操作人员暴露模型 (AOEM) 开始的主要活动，并涵盖了完善旁观者、居民和重新进入工人评估的现有方法的项目，包括旁观者居民果园葡萄园 (BROV) 项目、改进喷洒漂移旁观者和居民暴露评估模型 (BREAM)、完善蒸汽吸入评估的建议，以及可脱落叶面残留 (DFR) 数据的荟萃分析。此外，还介绍了一项对使用封闭式转移系统的益处进行量化的研究、对当前风险评估范例中固有的复合保守性的评估，以及 SeedTROPEX 工作组对新种子处理模型的开发。这些由行业主导的活动强调了非食用接触在购买力平价登记过程中的关键作用，并反映了在确保安全的同时为农民提供有效作物保护解决方案的持续承诺。

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引用次数: 0

Mutagenicity and genotoxicity evaluation of 15 nitrosamine drug substance-related impurities in human TK6 cells 15 种亚硝胺药物相关杂质在人类 TK6 细胞中的突变性和遗传毒性评估。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-20 DOI: 10.1016/j.yrtph.2024.105730

Xilin Li , Yuan Le , Xiaoqing Guo , Sruthi T. King , Robert T. Dorsam , Aisar H. Atrakchi , Timothy J. McGovern , Karen L. Davis-Bruno , David A. Keire , Robert H. Heflich , Nan Mei

Nitrosamine drug substance-related impurities (NDSRIs) are a sub-category of N-nitrosamine drug impurities that share structural similarity to the corresponding active pharmaceutical ingredient. The mutagenicity of NDSRIs is poorly understood. We previously tested a series of NDSRIs using the Enhanced Ames Test (EAT). In this follow-up study, we further examined the genotoxicity and mutagenicity of 15 of these NDSRIs in human TK6 cells. Seven EAT-positive NDSRIs, including N-nitroso-nortriptyline, N-nitroso-fluoxetine, N-nitroso-desmethyl-diphenhydramine, N-nitroso-duloxetine, N-nitroso-lorcaserin, N-nitroso-varenicline, and N-nitroso-sertraline, induced concentration-dependent increases in micronuclei after bioactivation with hamster liver S9. These NDSRIs were also mutagenic in the TK and HPRT gene mutation assays, consistent with their positive EAT results. In the presence of hamster liver S9, the eight EAT-negative NDSRIs were negative in the micronucleus assay and negative for mutation induction. Using TK6 cells endogenously expressing a single human cytochrome P450 (CYP), we found that CYP2C19, CYP2B6, CYP2A6, and CYP3A4 are key enzymes activating the genotoxicity and mutagenicity of these NDSRIs. Overall, the hamster S9-mediated TK6 cell mutagenicity results agreed with those observed in the EAT, indicating consistency in the mutagenic responses produced by NDSRIs across different testing systems. These data support the use of EAT for hazard identification and safety assessment of NDSRIs.

亚硝胺药物物质相关杂质（NDSRIs）是 N-亚硝胺药物杂质的一个亚类，与相应的活性药物成分具有结构相似性。人们对 NDSRIs 的致突变性知之甚少。我们曾使用增强艾姆斯试验（EAT）对一系列 NDSRIs 进行过测试。在这项后续研究中，我们进一步检测了其中 15 种 NDSRI 在人类 TK6 细胞中的遗传毒性和诱变性。七种 EAT 阳性的 NDSRIs（包括 N-亚硝基-去甲替普林、N-亚硝基-氟西汀、N-亚硝基-去甲二苯海拉明、N-亚硝基-度洛西汀、N-亚硝基-洛卡色林、N-亚硝基-伐尼克兰和 N-亚硝基-舍曲林）在与仓鼠肝脏 S9 进行生物活化后会诱发浓度依赖性的微核增加。在 TK 和 HPRT 基因突变试验中，这些 NDSRIs 也具有诱变性，这与它们的 EAT 阳性结果一致。在有仓鼠肝脏 S9 存在的情况下，8 种 EAT 阴性的 NDSRI 在微核试验中呈阴性，诱导突变的作用也呈阴性。利用内源表达单一人类细胞色素 P450（CYP）的 TK6 细胞，我们发现 CYP2C19、CYP2B6、CYP2A6 和 CYP3A4 是激活这些 NDSRIs 遗传毒性和诱变性的关键酶。总体而言，仓鼠 S9 介导的 TK6 细胞诱变性结果与在 EAT 中观察到的结果一致，表明 NDSRIs 在不同测试系统中产生的诱变反应具有一致性。这些数据支持使用 EAT 对 NDSRIs 进行危害识别和安全评估。

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引用次数: 0

Commentary: Understanding IARC's PFOA and PFOS carcinogenicity assessments 评论：了解 IARC 的 PFOA 和 PFOS 致癌性评估。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-19 DOI: 10.1016/j.yrtph.2024.105726

Nicholas L. Drury , Robyn L. Prueitt , Barbara D. Beck

In November 2023, the International Agency for Research on Cancer (IARC) classified PFOA as “carcinogenic to humans” (Group 1) and PFOS as “possibly carcinogenic to humans” (Group 2B). We evaluated these classifications, considering the epidemiology, experimental animal, and mechanistic evidence. It is our opinion that the IARC Working Group overstated the available evidence for the carcinogenicity of PFOA and PFOS. Epidemiology studies have shown weak and inconsistent associations across studies. Studies reporting increased incidences of tumors in experimental animals exposed to PFOA or PFOS had statistically significant results that were driven by the presence of benign adenomas. The IARC Working Group used the key characteristics of carcinogens (KCCs, which comprise 10 chemical and/or biological properties of known human carcinogens) approach to upgrade the carcinogenicity classifications for PFOA and PFOS from initially lower classifications that were based on the strength of the epidemiology and experimental animal evidence. However, this is not a robust assessment of mechanistic evidence, as it fails to consider the quality, external validity, and relevance of the evidence. Rather than use the KCCs as a checklist of potential carcinogenic mechanisms, IARC should use a rigorous method to evaluate the plausibility and human relevance of mechanistic evidence.

2023 年 11 月，国际癌症研究机构（IARC）将全氟辛烷磺酸列为 "对人类致癌"（第 1 类），将全氟辛烷磺酸列为 "可能对人类致癌"（第 2B 类）。我们对这些分类进行了评估，考虑了流行病学、实验动物和机理证据。我们认为，国际癌症研究机构工作组夸大了 PFOA 和 PFOS 致癌的现有证据。流行病学研究表明，不同研究之间的关联性较弱且不一致。报告暴露于全氟辛烷磺酸或全氟辛烷磺酸的实验动物肿瘤发病率增加的研究，其结果在统计学上具有显著意义，这是因为良性腺瘤的存在。国际癌症研究机构工作组采用致癌物关键特征（KCCs，由已知人类致癌物的 10 种化学和/或生物特性组成）的方法，将 PFOA 和 PFOS 的致癌性分类从最初的较低分类升级，而最初的较低分类是基于流行病学和实验动物证据的强度。然而，这并不是对机理证据的有力评估，因为它没有考虑证据的质量、外部有效性和相关性。国际癌症研究机构不应将 KCCs 用作潜在致癌机制的核对表，而应使用严格的方法来评估机理证据的合理性和与人类的相关性。

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引用次数: 0

An analysis of the use of historical control data in the assessment of regulatory pesticide toxicity studies 分析历史控制数据在农药毒性监管研究评估中的应用。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-18 DOI: 10.1016/j.yrtph.2024.105724

Jürg A. Zarn, Sebastian L.B. König, Holly V. Shaw, H. Christoph Geiser

The concurrent control group is the most important reference for the interpretation of toxicity studies. However, pooled information on control animals from independent studies, i.e., historical control data (HCD), is also used for the interpretation of results. Currently, an overview on actual HCD use in regulatory toxicology is lacking. Therefore, we evaluated the HCD use of the Joint FAO/WHO Meeting on Pesticide Residues from 2004 to 2021 and compared it with recommendations in regulatory guidelines and in the literature. We found that HCD was used routinely and exclusively to avoid potential false positive decisions regarding the treatment-relatedness of effects, mostly using the HCD range, i.e., the most extreme values, as a benchmark. HCD were not used to avoid potential false negative decisions or for quality control of the index study. The central assumption of the HCD use, namely that the HCD and control group of the index study follow the same underlying distribution because they are samples of the same data generation process, was not investigated, although numerous factors potentially contribute to effect variation between the different control groups pooled in the HCD. We recommend that the existing guidelines be revised to improve the robustness and transparency of toxicological assessments.

同期对照组是解释毒性研究的最重要参考。不过，来自独立研究的对照动物的汇总信息，即历史对照数据（HCD），也可用于解释研究结果。目前，监管毒理学中实际使用 HCD 的情况尚缺乏综述。因此，我们评估了 2004 年至 2021 年粮农组织/世卫组织农药残留联席会议使用 HCD 的情况，并将其与监管指南和文献中的建议进行了比较。我们发现，HCD 的常规使用完全是为了避免在影响的处理相关性方面可能出现的假阳性判定，大多使用 HCD 范围（即最极端值）作为基准。HCD 不用于避免潜在的假阴性判定，也不用于指标研究的质量控制。使用 HCD 的核心假设，即指数研究中的 HCD 和对照组遵循相同的基本分布，因为它们是同一数据生成过程中的样本，并没有进行调查，尽管有许多因素可能导致 HCD 中汇集的不同对照组之间的效应差异。我们建议修订现有指南，以提高毒理学评估的稳健性和透明度。

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引用次数: 0

In vivo micronucleus assay on sodium molybdate in rats and its impact on the overall assessment of the genotoxicity of molybdenum substances 钼酸钠大鼠体内微核试验及其对全面评估钼物质遗传毒性的影响。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-11 DOI: 10.1016/j.yrtph.2024.105717

Sue A. Hubbard , Kevin Klipsch , Michael S. Cockburn , Sandra Carey

In this paper we present methodological and experimental details and results from an OECD Test Guideline 474 and GLP-compliant in vivo micronucleus study on sodium molybdate dihydrate in Sprague Dawley rats. Prior to the conduct of this study, there was a data-gap for reliable in vivo genotoxicity data for molybdenum substances. The presentation of the new study is complemented by a review of other available in vitro and in vivo data on the genotoxicity of molybdenum substances, focussing on substances where the contained or released molybdate ion, MoO₄²⁻, is considered the responsible moiety for any toxicological effect (grouping/category approach). After consideration of the relevance and reliability of all available data, the absence of a concern for genotoxicity of molybdate in vitro and in vivo is concluded.

本文介绍了一项符合《经合组织测试指南 474》和 GLP 标准的体内微核试验研究的方法和实验细节，以及在 Sprague Dawley 大鼠体内对钼酸钠二水合物进行的研究结果。在开展这项研究之前，关于钼物质的可靠体内遗传毒性数据还存在空白。在介绍这项新研究的同时，我们还回顾了有关钼物质遗传毒性的其他现有体外和体内数据，重点是那些含有或释放的钼酸根离子MoO42-被认为是造成任何毒理效应的主要分子的物质（分组/分类方法）。在考虑了所有可用数据的相关性和可靠性后，得出结论认为钼酸盐在体外和体内不存在遗传毒性问题。

引用次数: 0

Analysis of implicit and explicit uncertainties in QSAR prediction of chemical toxicity: A case study of neurotoxicity 化学毒性 QSAR 预测中的隐式和显式不确定性分析：神经毒性案例研究。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-10 DOI: 10.1016/j.yrtph.2024.105716

Jerry Achar , James W. Firman , Chantelle Tran , Daniella Kim , Mark T.D. Cronin , Gunilla Öberg

Although uncertainties expressed in texts within QSAR studies can guide quantitative uncertainty estimations, they are often overlooked during uncertainty analysis. Using neurotoxicity as an example, this study developed a method to support analysis of implicitly and explicitly expressed uncertainties in QSAR modeling studies. Text content analysis was employed to identify implicit and explicit uncertainty indicators, whereafter uncertainties within the indicator-containing sentences were identified and systematically categorized according to 20 uncertainty sources. Our results show that implicit uncertainty was more frequent within most uncertainty sources (13/20), while explicit uncertainty was more frequent in only three sources, indicating that uncertainty is predominantly expressed implicitly in the field. The most highly cited sources included Mechanistic plausibility, Model relevance and Model performance, suggesting they constitute sources of most concern. The fact that other sources like Data balance were not mentioned, although it is recognized in the broader QSAR literature as an area of concern, demonstrates that the output from the type of analysis conducted here must be interpreted in the context of the broader QSAR literature before conclusions are drawn. Overall, the method established here can be applied in other QSAR modeling contexts and ultimately guide efforts targeted towards addressing the identified uncertainty sources.

虽然 QSAR 研究中文本表达的不确定性可以指导定量不确定性估计，但在不确定性分析过程中却经常被忽视。本研究以神经毒性为例，开发了一种支持分析 QSAR 建模研究中隐含和明确表达的不确定性的方法。我们采用文本内容分析法来识别隐式和显式不确定性指标，然后识别包含指标的句子中的不确定性，并根据 20 个不确定性来源进行系统分类。结果表明，在大多数不确定性来源（13/20）中，隐式不确定性更为常见，而显式不确定性仅在三个来源中更为常见，这表明不确定性在该领域主要以隐式表达。引用率最高的来源包括机理可信性、模型相关性和模型性能，这表明它们是最受关注的来源。数据平衡等其他来源虽然在更广泛的 QSAR 文献中被认为是一个值得关注的领域，但却没有被提及，这一事实表明，在得出结论之前，必须在更广泛的 QSAR 文献背景下对本文所做分析的结果进行解释。总之，本文所建立的方法可用于其他 QSAR 建模环境，并最终指导解决已确定的不确定性来源。

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引用次数: 0

Selection of solvent and positive control concentration for enhanced Ames test conditions for N-nitrosamine compounds 针对 N-亚硝胺化合物的强化 Ames 试验条件，选择溶剂和阳性对照浓度

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-10 DOI: 10.1016/j.yrtph.2024.105711

Chetan K. Kajavadara, Satyam N. Patel, Rushikesh M. Shukla, Darshan T. Valani, Rajesh J. Patel, Laxit K. Bhatt, Rajesh Sundar, Mukul R. Jain

The Ames test is a widely used bacterial mutagenicity assay to evaluate the potential of chemical compounds to induce mutations. In recent years, there has been growing concern regarding the presence of N-nitrosamines in pharmaceuticals, food, and other consumer products. N-Nitrosamines are probable mutagens and carcinogens. To address the reduced sensitivity of the standard Ames test for N-nitrosamines, particularly N-nitrosodimethylamine, the European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) have recently published recommendations for enhanced Ames test (EAT) conditions. However, there is a lack of clear guidance on the selection of N-nitrosamine positive control concentrations, particularly for 1-cyclopentyl-4-nitrosopiperazine, and the amount of solvent to be used in the EAT. This study aims to address the current gap in concentration and volume specifications by providing a comprehensive guide to set up enhanced Ames test conditions specifically for N-nitrosamine compounds using appropriate amounts of solvent, new solvents, and strain-specific positive control concentrations.

艾姆斯试验是一种广泛使用的细菌诱变性检测方法，用于评估化学物质诱发突变的可能性。近年来，人们越来越关注药品、食品和其他消费品中是否含有 N-亚硝胺。亚硝胺可能是诱变剂和致癌物质。为了解决亚硝胺（尤其是 N-亚硝基二甲胺）标准阿姆斯试验灵敏度降低的问题，欧洲药品管理局 (EMA) 和美国食品药品管理局 (FDA) 最近公布了关于增强型阿姆斯试验 (EAT) 条件的建议。然而，在选择 N-亚硝胺阳性对照浓度（尤其是 1-环戊基-4-亚硝基哌嗪）和 EAT 中使用的溶剂量方面缺乏明确的指导。本研究旨在解决目前在浓度和体积规范方面的空白，提供一份综合指南，指导如何使用适当的溶剂量、新溶剂和特定菌株的阳性对照浓度，专门针对 N-亚硝胺化合物建立增强型艾姆斯试验条件。

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引用次数: 0

Safety assessment of drug impurities for patient safety: A comprehensive review 针对患者安全的药物杂质安全评估：全面综述。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-05 DOI: 10.1016/j.yrtph.2024.105715

Frank Liu

Drug impurities are undesirable but unavoidable chemicals which can occur throughout the drug life cycle. The safety implications of drug impurities can be significant given that they can impact safety, quality, and efficacy of drug products and that certain drug impurities are mutagenic, carcinogenic, or teratogenic. The characteristics of drug impurities could be specific to drug modalities (e.g., small molecules vs. biologics). The commonly encountered drug impurities include elemental impurity, residual solvent, organic impurity, host cell protein and DNA, residual viral vector, extractable and leachable, and particle. They can cause various adverse effects such as immunogenicity, infection, genotoxicity, and carcinogenicity upon significant exposure. Therefore, the effective control of these drug impurities is central for patient safety. Regulations and guidelines are available for drug developers to manage them. Their qualification is obtained based on authoritative qualification thresholds or safety assessment following the classic toxicological risk assessment. The current review focuses on the safety assessment science and methodology used for diverse types of drug impurities. Due to the different nature of diverse drug impurities, their safety assessment represents a significant challenge for drug developers.

药物杂质是在整个药物生命周期中可能出现的不良但不可避免的化学物质。鉴于药物杂质会影响药物产品的安全、质量和疗效，而且某些药物杂质具有致突变、致癌或致畸作用，因此药物杂质对安全的影响可能非常大。药物杂质的特征可能因药物方式（如小分子药物与生物制剂）而异。常见的药物杂质包括元素杂质、残留溶剂、有机杂质、宿主细胞蛋白和 DNA、残留病毒载体、可提取和可浸出物以及颗粒。这些杂质一旦大量接触，就会产生各种不良反应，如免疫原性、感染、基因毒性和致癌性。因此，有效控制这些药物杂质对患者安全至关重要。目前已有相关法规和指南供药物开发商管理这些杂质。它们的合格性是根据权威的合格阈值或按照经典的毒理学风险评估进行的安全性评估而获得的。本综述重点关注用于不同类型药物杂质的安全性评估科学和方法。由于各种药物杂质的性质不同，其安全性评估对药物开发人员来说是一项重大挑战。

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引用次数: 0

Quantitative risk assessments of skin sensitization for 26 allergens in different consumer products in the Saudi market 对沙特市场不同消费品中的 26 种过敏原进行皮肤过敏定量风险评估。

IF 3 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2024-10-03 DOI: 10.1016/j.yrtph.2024.105714

Adnan S. AL-Mussallam , Rawan S. Alshathri , Bart Desmedt , Fahad S. Aldawsari , Eric Deconinck , Omniyah A. Alharthi , Abdullah T. Bawazir

Fragrance chemicals are ubiquitous in cosmetics; however, they have been linked to allergic contact dermatitis. Allergy prevention involves two main strategies. Firstly, consumers are protected by limiting the maximum concentration of fragrance in a given product to avoid inducing allergies. Secondly, consumers who are already sensitized are protected by having the presence of such fragrance communicated to them. In this study, a validated GC-MS method was employed to quantify 26 allergens in 108 products marketed in Saudi Arabia.Additionally, a quantitative risk assessment (QRA) was performed on the studied cosmetics to determine the risk of inducing allergies. The results indicated that most allergens were present at acceptable concentrations, while 19 products carried a risk of inducing allergies. Furthermore, Lilial and Lyral, two prohibited fragrances, were detected in 97 products. It should be emphasized that this is the first study conducted in Saudi Arabia to evaluate the safety of the well-known 26 fragrance allergens. Hence, this study can potentially serve as a regional standard for future research.

香料化学物质在化妆品中无处不在，但它们却与过敏性接触性皮炎有关。预防过敏主要有两种策略。首先，通过限制特定产品中香料的最大浓度来保护消费者，避免诱发过敏。其次，对于已经过敏的消费者，可以通过告知他们产品中含有此类香料来保护他们。此外，还对所研究的化妆品进行了定量风险评估 (QRA)，以确定诱发过敏的风险。结果表明，大多数过敏原的浓度在可接受范围内，而 19 种产品有诱发过敏的风险。此外，在 97 种产品中检测到了 Lilial 和 Lyral 这两种禁用香料。需要强调的是，这是沙特阿拉伯首次对众所周知的 26 种香料过敏原的安全性进行评估。因此，这项研究有可能成为未来研究的地区标准。

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引用次数: 0