Regulatory Toxicology and Pharmacology最新文献_第7页

The Decision Tree approach as a strategy for the global phase out of animal testing for acute and local toxicity for chemicals: recommendations from an expert workshop 决策树方法作为全球逐步淘汰化学品急性毒性和局部毒性动物试验的战略：专家讲习班的建议。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-10-22 DOI: 10.1016/j.yrtph.2025.105969

Catherine Willett , Giorgia Pallocca , Annamaria Carusi , Nathalie Alépée , Patience Browne , Marie Darracq-Ghitalla-Ciock , Fabian A. Grimm , Jay Ingram , Laura Holden , Kamel Mansouri , Hans Raabe , Clive Roper , Katherine Santizo , Barbara G. Schmitt , Li Xiang , Thomas A. Ward , Bryan Zhou

The Animal-Free Safety Assessment (AFSA) Collaboration invited a select group of international experts, representing regulatory bodies, industry, method developers, and academia, to a workshop to develop a regulatory strategy implementing non-animal approaches to assess acute toxicity endpoints. The workshop, held in Loch Lomond, Scotland, from 28 April to 1 May, 2025, aimed to develop a decision tree (DT) approach that could support the implementation of non-animal methods and the phased-out use of animal testing for systemic acute and local toxicity.

This DT approach provides a transparent decision-making workflow that assists users in applying appropriate opportunities for waiving testing, non-animal testing methods (NAMs), and other adaptations consistently across chemical regulations. DTs also serve to increase awareness of the application of non-animal approaches and ensure compliance with the last resort requirement for animal studies. This workshop aimed to review the suitability of the proposed framework, formulate overarching recommendations for its implementation and provide specific feedback and timelines to finalise endpoint-specific DTs for acute oral toxicity, eye irritation and corrosion, skin irritation and corrosion, and skin sensitisation. This report summarises the overarching discussions and findings tackled during the meeting. The individual endpoint-specific DTs will be described in follow-up scientific publications.

无动物安全评估（AFSA）合作组织邀请了一组精选的国际专家，代表监管机构、工业界、方法开发者和学术界，参加一个研讨会，制定一项实施非动物方法评估急性毒性终点的监管战略。该研讨会于2025年4月28日至5月1日在苏格兰Loch Lomond举行，旨在制定一种决策树（DT）方法，支持实施非动物方法，并逐步淘汰用于全身急性和局部毒性的动物试验。这种DT方法提供了一个透明的决策工作流程，帮助用户应用适当的机会来放弃测试，非动物测试方法（NAMs），以及跨化学品法规一致的其他适应性。DTs还有助于提高对非动物方法应用的认识，并确保遵守动物研究的最后手段要求。本次研讨会旨在审查拟议框架的适用性，为其实施制定总体建议，并提供具体的反馈和时间表，以最终确定急性口服毒性，眼睛刺激和腐蚀，皮肤刺激和腐蚀以及皮肤致敏的终点特异性DTs。本报告总结了会议期间的主要讨论和结果。个别特定终点的DTs将在后续科学出版物中进行描述。

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引用次数: 0

Case studies on skin sensitization risk assessment: estimating the PoD using artificial neural network-based models for substances with known and unknown structure 皮肤致敏风险评估的案例研究：使用基于人工神经网络的模型估算已知和未知结构物质的PoD。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-10-22 DOI: 10.1016/j.yrtph.2025.105978

Kosuke Imai , Yuri Hatakeyama , Tomomi Atobe, Toshiyuki Ohtake, Shiho Oeda, Morihiko Hirota

Non-animal methods for skin sensitization assessment have been developed and adopted as OECD test guidelines. However, no single new approach methodology (NAM) can fully replace animal-based methods, leading to the development of defined approaches like OECD GL497. This study advances quantitative risk assessment (QRA) for skin sensitization using Artificial Neural Network (ANN) models to predict LLNA EC3 values. As a case study, six substances were evaluated using ANN models based on the Direct Peptide Reactivity Assay (DPRA) and the Amino acid Derivative Reactivity Assay (ADRA). These substances included four with known structures (Metol, Dibenzyl Ether, Safranal, and Lyral) and two with unknown structures (Verbena Oil and Oakmoss Extract). Most predicted EC3 values were within a 10-fold range of observed values, demonstrating model reliability. Incorporating ADRA molar and gravimetric method data, ANN models successfully predicted EC3 values for both substances with known and unknown structure, showing their applicability to natural complex substances like botanical extracts. A new skin sensitization risk assessment flow incorporating ANN models is proposed, contributing to the 3Rs by providing a reliable, non-animal method for determining Points of Departure (PoD) and advancing Next Generation Risk Assessment (NGRA) for cosmetic ingredients.

非动物皮肤致敏评估方法已被开发并采纳为经合组织的测试指南。然而，没有一种新的方法方法（NAM）可以完全取代基于动物的方法，这导致了像OECD GL497这样的明确方法的发展。本研究利用人工神经网络（ANN）模型预测皮肤致敏的定量风险评估（QRA）来预测LLNA EC3值。作为案例研究，采用基于直接肽反应性测定（DPRA）和氨基酸衍生物反应性测定（ADRA）的人工神经网络模型对6种物质进行了评价。这些物质包括四种已知结构的物质（甲醇、二苯醚、番红花醛和Lyral）和两种未知结构的物质（马鞭草油和橡苔提取物）。大多数预测的EC3值在观测值的10倍范围内，证明了模型的可靠性。结合ADRA摩尔和重量法数据，ANN模型成功预测了已知和未知结构物质的EC3值，显示了其对植物提取物等天然复杂物质的适用性。本文提出了一种新的基于神经网络模型的皮肤致敏风险评估流程，通过提供一种可靠的、非动物的方法来确定出发点（PoD），并推进化妆品成分的下一代风险评估（NGRA），为3r做出了贡献。

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引用次数: 0

Physiologically based pharmacokinetic modeling of oseltamivir in pregnant rhesus macaques to inform clinical dosing across trimesters 基于生理的奥司他韦在妊娠恒河猴体内的药代动力学建模，为临床用药提供信息。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-10-22 DOI: 10.1016/j.yrtph.2025.105979

Darshan Mehta, Kiara Fairman, Miao Li , Jeffrey Fisher , Frederick A. Beland, Gonçalo Gamboa da Costa, Annie Lumen

Oseltamivir phosphate is a lipophilic prodrug that is metabolized to the active form, oseltamivir carboxylate, by carboxylesterase 1 enzymes in the liver in humans and in the liver and gut in rhesus macaques. Oseltamivir carboxylate is hydrophilic and distributes extensively in extracellular fluids, including plasma, and is eliminated primarily by the kidneys through glomerular filtration and tubular secretion. Pregnant women have lower systemic exposure to oseltamivir carboxylate due to an increase in plasma volume and total body water, leading to an increased apparent volume of distribution and increased renal excretion. To evaluate the differences in oseltamivir pharmacokinetics during pregnancy, a study was conducted previously using rhesus monkeys that were administered oseltamivir phosphate via intravenous and nasogastric routes at doses of 2.5 mg/kg body weight during the three trimesters of pregnancy. In the current study, we present a physiologically based pharmacokinetic (PBPK) model to help characterize the pharmacokinetic data that were collected in the previous study and demonstrate how the model can be used to predict the pharmacokinetics of oseltamivir and oseltamivir carboxylate in pregnant women. As it can be challenging to obtain rich clinical data in pregnant women, evaluating drug pharmacokinetics in preclinical species using tools such as PBPK models can provide reliable estimates of drug disposition across species during sensitive life stages such as pregnancy. Using the PBPK modeling approach, we were able to successfully characterize a reduction in oseltamivir carboxylate exposure during pregnancy in rhesus macaques (20–25 % decrease in AUC) and satisfactorily extend the model predictions to humans by accounting for physiological changes that occur throughout the different stages of pregnancy. The rhesus macaque can thus be considered a promising animal model for extrapolating pharmacokinetic predictions during pregnancy, especially for drugs or chemicals that are metabolized by hydrolysis reactions and primarily eliminated by renal excretion.

磷酸奥司他韦是一种亲脂性前药，在人类肝脏和猕猴肝脏和肠道中通过羧酸酯酶1代谢成活性形式奥司他韦羧酸奥司他韦。羧酸奥司他韦具有亲水性，广泛分布于包括血浆在内的细胞外液中，主要由肾脏通过肾小球滤过和肾小管分泌排出。孕妇由于血浆容量和全身水分增加，全身暴露于奥司他韦羧酸盐较低，导致表观分布体积增加和肾排泄增加。为了评估妊娠期间奥司他韦药代动力学的差异，之前对恒河猴进行了一项研究，这些恒河猴在妊娠三个月期间通过静脉注射和鼻胃给药，剂量为2.5 mg/kg体重。在当前的研究中，我们提出了一个基于生理的药代动力学（PBPK）模型，以帮助描述先前研究中收集的药代动力学数据，并证明该模型如何用于预测奥司他韦和奥司他韦羧酸盐在孕妇中的药代动力学。由于在孕妇中获得丰富的临床数据可能具有挑战性，使用PBPK模型等工具评估临床前物种的药物药代动力学可以提供在敏感生命阶段（如怀孕）跨物种药物配置的可靠估计。使用PBPK建模方法，我们能够成功地描述猕猴怀孕期间奥司他韦羧酸盐暴露的减少（AUC降低20 - 25%），并通过考虑整个怀孕不同阶段发生的生理变化，将模型预测满意地扩展到人类。因此，恒河猴可以被认为是一种很有前途的动物模型，用于推断怀孕期间的药代动力学预测，特别是对于通过水解反应代谢并主要通过肾脏排泄消除的药物或化学物质。

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引用次数: 0

Evaluation of 13-week repeated-dose oral toxicity of zirconium(IV) butoxide in Crl:CD(SD) rats 丁二氧化锆（IV）对CD（SD）大鼠13周重复剂量口服毒性评价。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-10-21 DOI: 10.1016/j.yrtph.2025.105968

Yasumasa Murata , Jun-ichi Akagi , Yuko Doi , Takako Iso , Takaaki Umano , Kenichi Masumura , Mariko Matsumoto , Takeshi Toyoda , Kumiko Ogawa

Zirconium(IV) butoxide (ZB; CAS 1071-76-7) is widely used in industrial applications as a catalyst, stabilizer, and precursor for ceramic materials utilized in medical devices such as artificial bones and teeth. Metal alkoxide compounds, including ZB, are easily hydrolyzed, polymerized, and precipitated in aqueous environments. Although a no-observed-adverse-effect level (NOAEL) for ZB has been estimated by extrapolating its hydrolysis product, 1-butanol, ZB toxicological profile remains unclear, leaving data gaps for risk evaluation. In this study, we developed a method for ZB preparation and administration using corn oil as vehicle, in which ZB was retained its polymerizable form. A 13-week repeated-dose oral toxicity study was conducted in 6-week-old Crl:CD(SD) rats. Groups of ten males and females were orally administered ZB at doses of 0 (vehicle: corn oil), 100, 300, and 1000 mg/kg body weight (bw)/day, or 1-butanol at 116 mg/kg bw/day, which was equivalent to its level after dosing ZB at 1000 mg/kg bw/day. No toxicologically significant effects were observed after ZB administration. The NOAEL for ZB was estimated to be 1000 mg/kg bw/day in both sexes. These results provide essential toxicological data for safety assessment and regulatory evaluation of ZB.

丁二氧化锆（ZB; CAS 1071-76-7）作为催化剂、稳定剂和前驱体广泛应用于医疗器械（如人造骨和牙齿）的陶瓷材料。金属醇氧化合物，包括ZB，在水环境中很容易水解、聚合和沉淀。虽然通过外推其水解产物- 1-丁醇估计了ZB的无观察到的不良反应水平（NOAEL），但ZB的毒理学特征仍不清楚，为风险评估留下了数据空白。在本研究中，我们开发了一种以玉米油为载体的ZB制备和给药方法，该方法保留了ZB的可聚合形式。对6周龄大鼠进行了为期13周的重复给药口服毒性研究。每组10只雄性和雌性分别口服剂量为0、100、300和1,000 mg/kg体重(bw)/天的ZB（对照剂：玉米油），或剂量为116 mg/kg体重/天的1-丁醇，其剂量与ZB剂量为1,000 mg/kg体重/天后的水平相当。ZB给药后未见明显毒理学效应。两性对ZB的NOAEL估计为1,000 mg/kg bw/day。这些结果为ZB的安全性评价和监管评价提供了必要的毒理学数据。

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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 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub 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

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.

由于环境的限制、操作人员的可变性以及现有模型在实际工作条件下的有限适用性，对温室植物保护产品职业暴露的准确评估提出了具体的挑战。本研究提出了一种数字工具的开发，该工具实现了评估温室工人农药暴露风险的半定量模型。该模型集成了四种暴露场景中的特定任务变量：混合和加载、应用程序、维护和重新进入；并应用对数评分系统来计算暴露指数。然后将该指数与从产品危害分类中得出的毒性评分相结合，以获得综合风险水平，使用具有相应预防建议的五层分类方案进行解释。该申请包括一份初步调查问卷，以确保满足基本的安全条件，并包含一个自动更新机制，根据官方注册表维护最新的授权产品清单。该工具的开发重点是可用性和结构化逻辑，支持有效的数据输入和结果的可解释性。在西班牙东南部的不同温室进行了现场测试，验证了该工具在实际条件下的一致性和功能性。

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引用次数: 0

Exposure and disease burden of fumonisins and aflatoxins from sorghum consumption in Ethiopia 埃塞俄比亚食用高粱中伏马菌素和黄曲霉毒素的暴露和疾病负担。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-10-14 DOI: 10.1016/j.yrtph.2025.105966

J.A. Sadik , N. Fentahun , I.D. Brouwer , M. Tessema , H.J.van der Fels-Klerx

Studies on mycotoxin exposure from sorghum consumption and related public health risk estimation are rarely available in Ethiopia. The aim of this research was to assess fumonisin and aflatoxin exposure of adults through sorghum consumption in the Amhara National Regional State (ANRS) and at national level in Ethiopia and to estimate related health risks. Data on fumonisin and aflatoxin concentrations in sorghum samples were collected from a survey and literature. Estimated fumonisin exposure in the ANRS and at national level were below the FAO/WHO limit of 2000 ng/kg bw day to be considered a health concern. The estimated aflatoxin exposure levels in the ANRS and at national level fall below the Margin of Exposure value of 10000, indicating potential health concern. The incidence of hepatocellular carcinoma due to aflatoxin exposure in the ANRS ranges from 0.0003 to 0.017 while at national level, it ranges from 0.181 to 8.47 (per100.000 persons/year). The related disability-adjusted life years estimates for the ANRS and at national level ranged from 0.0003 to 0.019 and 0.204 to 11.230, respectively. Aflatoxin exposures were driven more by sorghum intake than aflatoxin contamination. Dietary intervention could further reduce the health risk estimates.

在埃塞俄比亚，很少有关于食用高粱引起的霉菌毒素暴露和相关公共卫生风险评估的研究。本研究的目的是评估阿姆哈拉民族地区州（ANRS）和埃塞俄比亚国家一级成年人通过食用高粱接触伏马菌素和黄曲霉毒素的情况，并估计相关的健康风险。高粱样品中伏马菌素和黄曲霉毒素浓度的数据从调查和文献中收集。在ANRS和国家一级估计的伏马菌素暴露量低于粮农组织/世卫组织每天2000纳克/公斤体重被视为健康问题的限值。在ANRS和国家一级估计的黄曲霉毒素暴露水平低于10000的暴露限度值，表明潜在的健康问题。在ANRS中，黄曲霉毒素暴露导致的肝细胞癌发病率为0.0003至0.017，而在全国水平上，这一发病率为0.181至8.47（每10万人/年）。ANRS和国家水平的相关残疾调整寿命年估计值分别在0.0003至0.019和0.204至11.230之间。与黄曲霉毒素污染相比，高粱摄入量更能驱动黄曲霉毒素暴露。饮食干预可以进一步降低健康风险估计。

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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 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub 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

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 in vitro-based regression models.

Herein, a framework for incorporating regression models into next-generation risk assessment (NGRA) is presented. The framework begins with hazard assessment using in vitro 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, p-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 in vitro models. This approach offers a promising alternative for PoD derivation, potentially eliminating the dependence on in-vivo data.

皮肤致敏的定量风险评估（QRA）对于确定消费品中皮肤致敏剂的安全浓度至关重要。香料行业开发了QRA2方法，该方法使用无预期致敏诱导水平（NESIL）作为起始参考剂量或出发点（PoD）。已经出现了用于效价评估的动物替代品来计算定量pod。其中一种选择是基于体外的回归模型。本文提出了一个将回归模型纳入下一代风险评估（NGRA）的框架。该框架首先使用体外方法进行危害评估（OECD指南497），然后通过回归模型计算PoD，最后使用QRA2完成。在确定PoD后，考虑不确定性因素可以推导出一种新的方法NESIL （NAM-NESIL）。案例研究采用两种致敏剂，对薄荷-1,8-二烯-7-al （CAS # 2111-75-3）和3-丙基酞（CAS # 17369-59-4），计算除臭剂和肥皂等产品的可接受暴露水平（AELs）。然后计算AELs与消费者暴露水平（CELs）的比率，以确定当前的使用是否安全。基于NAM-NESILs的QRA与历史上人类来源的NESILs的比较支持体外模型的可靠性。这种方法为PoD衍生提供了一种有希望的替代方法，有可能消除对动物数据或确认性人体测试的需求。

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引用次数: 0

Using read-across to identify isobutylparaben as an endocrine disruptor 使用读取识别对羟基苯甲酸异丁酯为内分泌干扰物。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-10-13 DOI: 10.1016/j.yrtph.2025.105965

Hanna KL. Johansson, Anna Kjerstine Rosenmai, Julie Boberg, Monica K. Draskau, Marie Louise Holmer, Terje Svingen, Marta Axelstad

引用次数: 0

Evaluating the ability of defined approaches to predict the human skin sensitisation potential of chemicals previously untested in new approach methodologies 评估已定义的方法预测以前未在新方法方法中测试的化学品的人体皮肤致敏潜力的能力。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-10-13 DOI: 10.1016/j.yrtph.2025.105963

Martyn L. Chilton , Tasha Jones , Adrian Fowkes , Donna S. Macmillan , Darren Kidd

Much progress has been made in the development and validation of New Approach Methodologies (NAMs) for assessing skin sensitisation, as part of the global move away from animal testing. While there are now numerous in silico models and in chemico/in vitro assays available, none are currently thought to be a one-for-one replacement for the animal tests, but rather several NAMs are combined within a Defined Approach (DA), such as those described in OECD guideline 497. In this study, 22 chemicals were chosen which have known human sensitisation potential, but which have not previously been tested in NAMs, to the best of the authors’ knowledge. New in chemico/in vitro data were generated for each chemical in three assays, and this was combined with in silico predictions from two models to generate predictions from four DAs. The data was used to assess the performance of the individual NAMs and DAs within a less well understood area of chemical space, and to learn more about their applicability domains. The newly generated data are made available herein in the expectation that they will be useful to others who are developing and/or validating DAs which assess the risk of chemicals causing human skin sensitisation.

作为全球从动物试验转向动物试验的一部分，在评估皮肤致敏的新方法方法（NAMs）的开发和验证方面取得了很大进展。虽然现在有许多可用的计算机模型和化学/体外测定，但目前没有一种被认为是动物试验的一对一替代，而是在确定方法（DA）中结合了几种nama，例如经合组织指南497中描述的方法。在这项研究中，据作者所知，选择了22种已知具有人类致敏潜力的化学物质，但这些化学物质以前没有在NAMs中进行过测试。在三次分析中为每种化学物质生成新的化学/体外数据，并将其与来自两个模型的计算机预测相结合，从四个DAs中生成预测。这些数据被用来评估单个NAMs和da在化学空间中不太为人所知的区域的性能，并更多地了解它们的适用领域。在此提供新生成的数据，期望它们对正在开发和/或验证评估化学物质引起人体皮肤致敏风险的DAs的其他人有用。

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引用次数: 0

Occupational asthma: dust exposure as a contributory factor and implications for classification of respiratory sensitisers 职业性哮喘：粉尘暴露作为一个促成因素和对呼吸道致敏物分类的影响。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-10-13 DOI: 10.1016/j.yrtph.2025.105962

Mark A. Pemberton , Ian Kimber

Occupational asthma (AO) is an important chronic respiratory disease associated with airway narrowing. Chemicals that cause OA are regulated under the UN GHS endpoint of respiratory sensitisation. Such chemicals are typically identified using evidence suggesting work-related exposure resulting in the ab initio development of asthma, rather than simply aggravating pre-existing asthma (work exacerbated asthma; WEA). There exist predisposing and aggravating factors within and outside the workplace that influence the development and severity of the disease. Inhalation exposure to dusts is one factor and is recognised as directly causing respiratory disease, and also aggravating pre-existing disease, including asthma. Here the contribution of dusts to the development of work-related asthma has been re-examined with reference to published clinical case studies. The data reveal a link between exposure to dusts and OA, suggesting an additional role of dust in this respect may be the presentation of irritant or sensitising agents in a way that promotes the development of OA, even under conditions where exposure to those agents alone does not. We propose that the significance of co-exposure to dusts may be currently under-estimated in health management of OA, clinical identification of chemicals suspected of causing OA, and classification of true respiratory sensitisers.

职业性哮喘（AO）是一种与气道狭窄相关的重要慢性呼吸系统疾病。引起OA的化学物质受联合国GHS呼吸道致敏终点的管制。这些化学物质通常是通过证据来确定的，这些证据表明与工作有关的接触会导致哮喘从头开始发展，而不是简单地加重已有的哮喘（工作加剧哮喘；WEA）。工作场所内外存在诱发和加重因素，影响疾病的发展和严重程度。吸入粉尘是一个因素，被认为是直接导致呼吸系统疾病的因素，也会加重已有的疾病，包括哮喘。在这里，粉尘对与工作相关的哮喘的发展的贡献已经参照已发表的临床病例研究进行了重新检查。数据揭示了接触粉尘与OA之间的联系，表明粉尘在这方面的另一个作用可能是以促进OA发展的方式呈现刺激性或致敏剂，即使在单独接触这些剂不会产生这种作用的情况下也是如此。我们认为，目前在OA的健康管理、疑似导致OA的化学物质的临床鉴定以及真正的呼吸致敏物分类方面，共暴露于粉尘的重要性可能被低估了。

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引用次数: 0