Regulatory Toxicology and Pharmacology最新文献_第4页

Methoxyflurane exposure in ambulances: a controlled laboratory study on paramedic safety 救护车中甲氧基氟醚暴露：护理人员安全的对照实验室研究。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-12-11 DOI: 10.1016/j.yrtph.2025.106012

Michael A. Austin , Somalin Mao , Jonathan MacLeod , Zachary Cantor

Methoxyflurane, a self-administered fluorinated hydrocarbon, provides rapid, relief for traumatic pain. While low-dose methoxyflurane poses minimal risk, paramedics may experience intermittent exposure. This study assesses occupational risks to enhance paramedic safety, health standards, and patient care directives.

Active air sampling was conducted in a Ministry of Health-approved ambulance, in the driver and patient compartment, under controlled conditions, both with and without ventilation. Twelve healthy participants inhaled for 15 min, with samples collected per EPA and ISO standards. Results were adjusted for time weighted average (TWA) exposure.

Twenty-four air samples were collected (median age 30.5 years, 50 % female). Exposure concentrations remained below 8-h TWA occupational limits and NIOSH 60-min ceiling limits. With ventilation, 8-h TWA levels were 0.001 ppm (driver) and 0.033 ppm (patient compartment), rising to 0.017 ppm and 0.057 ppm without ventilation. Maximum TWA levels for 22 transports (30-min duration) reached 0.019 ppm (driver) and 0.736 ppm (patient) with ventilation, increasing to 0.377 ppm and 1.254 ppm without. These were based upon worst-case assumptions of 22 treatment and transport events, each lasting 30 min, over a 12 h work shift. Ventilation significantly reduced exposure, with 99.1 % protocol adherence and no adverse events.

This controlled study confirms methoxyflurane's safe use in ambulances with exposure well below safety thresholds. Ventilation minimizes potential risk(s), ensuring paramedic safety and uninterrupted pain management.

甲氧基氟醚是一种自行使用的氟化碳氢化合物，能迅速缓解创伤性疼痛。虽然低剂量甲氧基氟醚的风险最小，但护理人员可能会间歇性接触。本研究评估职业风险，以提高护理人员的安全、健康标准和病人护理指示。在一辆卫生部批准的救护车上，在驾驶员和病人车厢内，在受控条件下进行了主动空气采样，有和没有通风。12名健康参与者吸入15分钟，并根据EPA和ISO标准收集样本。结果根据时间加权平均（TWA）暴露进行调整。收集了24份空气样本（中位年龄30.5岁，50%为女性）。暴露浓度仍低于8小时TWA职业限值和NIOSH 60分钟上限限值。在通风条件下，8小时TWA水平为0.001 ppm（驾驶员）和0.033 ppm（患者室），在不通风的情况下上升到0.017 ppm和0.057 ppm。22次运输（持续时间30分钟）的最大TWA水平在有通风的情况下达到0.019 ppm（驾驶员）和0.736 ppm（患者），在没有通风的情况下增加到0.377 ppm和1.254 ppm。这些是基于22个治疗和运输事件的最坏情况假设，每个事件持续30分钟，超过12小时的轮班。通气显著减少暴露，99.1%的人遵守协议，无不良事件发生。这项对照研究证实，甲氧基氟醚在远低于安全阈值的救护车中使用是安全的。通气可将潜在风险降至最低，确保护理人员安全和不间断的疼痛管理。

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引用次数: 0

Use of human data for risk assessment of pesticides: A review including an evaluation of trichlorfon as case study 使用人类数据进行农药风险评估：一项审查，包括对敌百虫作为个案研究的评价。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-12-09 DOI: 10.1016/j.yrtph.2025.106011

Giulia Collatuzzo , Paolo Boffetta

Pesticides are suspected to cause health effects in humans, but human-based data on their toxicity are often insufficient to establish associations and quantify risks. We reviewed literature on trichlorfon and investigated methodological aspects of risk assessment for pesticides based on human data. We provided an overview of epidemiology of pesticide toxicity, with focus on methodological features of the available studies, combined with a systematic review of the health effects of the pesticide, trichlorfon in humans, focusing on studies published after 1990. Studies on dichlorvos, the metabolite of trichlorfon, as well as metrifonate, a medication with the identical formula as trichlorfon, were included. A total of 60 publications were identified on health effects of trichlorfon, dichlorvos and metrifonate. Studies on acute effects (N = 23 publications) comprised mainly case-reports related to accidents and suicidal attempts, and were connoted by cholinergic syndrome, gastrointestinal and general symptoms. Evidence on chronic effects derived from analyses of the Agricultural Health Study (28 publications), as well as case-control and cross-sectional studies (9 publications). Evidence of possible associations between trichlorfon or dichlorvos exposure and various outcomes was heterogeneous and insufficient to establish causality. Critical features of epidemiology studies used for pesticide risk assessment include study design, exposure misclassification, lack of quantitative exposure data, and lack of consideration to potential confounders. Few high-quality epidemiology studies are available on potential health effects of trichlorfon. Future studies conducted according to established guidelines and supported by artificial intelligence might help to fill the gap on human health risks from pesticides.

农药被怀疑对人类健康造成健康影响，但基于人类的毒性数据往往不足以建立关联和量化风险。我们回顾了有关敌百虫的文献，并调查了基于人体数据的农药风险评估的方法学方面。我们概述了农药毒性的流行病学，重点介绍了现有研究的方法学特点，并对农药敌百虫对人类健康的影响进行了系统审查，重点介绍了1990年以后发表的研究。对敌百虫的代谢物敌敌畏以及配方与敌百虫相同的药物三氟膦酸盐进行了研究。共确定了60份关于敌百虫、敌敌畏和三氟膦酸盐对健康影响的出版物。关于急性效应的研究（N=23篇出版物）主要包括与事故和自杀企图有关的病例报告，并伴有胆碱能综合征、胃肠道和一般症状。关于慢性影响的证据来自农业健康研究（28篇出版物）以及病例对照和横断面研究（9篇出版物）的分析。暴露于敌百虫或敌敌畏与各种结果之间可能存在关联的证据参差不齐，不足以确定因果关系。用于农药风险评估的流行病学研究的关键特征包括研究设计、暴露错误分类、缺乏定量暴露数据以及缺乏对潜在混杂因素的考虑。关于敌百虫对健康的潜在影响的高质量流行病学研究很少。未来根据既定准则并在人工智能支持下进行的研究可能有助于填补农药对人类健康风险的空白。

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引用次数: 0

Subchronic oral toxicity and genotoxicity of Aurantii Fructus Immaturus water extract 枳实水提取物的亚慢性口服毒性及遗传毒性研究。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-12-09 DOI: 10.1016/j.yrtph.2025.106010

So-Young An , Si-Whan Song , Hyun-Suk Heo , Chang-Wok Park , Min-Sub Kim , Woo-Joo Lee , Yoo-Jin Park , Jae-Ho Shin , Beom Seok Han , Wan-Seob Cho

Aurantii Fructus Immaturus (AFI) water extract has been utilized in traditional medicine; however, its toxicity data are still lacking. In this study, we evaluated the general and genetic toxicity of the AFI water extract as a project of the Korea National Toxicology Program (KNTP). Naringin and neohesperidin, marker compounds of AFI, contained in the AFI water extract were 7.63 % and 4.51 %, respectively. These levels were higher than AFI powders, which contain about 4 % naringin and 3 % neohesperidin. The acute oral toxicity study in rats, conducted at doses of 2500–10000 mg/kg, demonstrated that the median lethal dose (LD₅₀) of AFI water extract exceeds 10000 mg/kg. Subacute oral toxicity tests at doses up to 5000 mg/kg/day and subchronic toxicity studies conducted over 13 weeks at similar dose ranges showed no treatment-related adverse effects. Thus, the no-observed-adverse-effect level (NOAEL) of AFI water extract in rats was 5000 mg/kg bw/day. Additionally, three genotoxicity assays (bacterial reverse mutation, in vitro chromosomal aberration, and in vivo micronucleus tests) confirmed that the AFI water extract is not genotoxic. These results will provide the toxicity data for the risk assessment of AFI water extract for human consumption.

枳实（AFI）水提物已被广泛应用于传统医学；然而，其毒性数据仍然缺乏。在本研究中，作为韩国国家毒理学计划（KNTP）的一个项目，我们评估了AFI水提取物的一般毒性和遗传毒性。AFI水提物中柚皮苷和新橙皮苷的含量分别为7.63%和4.51%。这些含量高于AFI粉末，后者含有约4%的柚皮苷和3%的新橙皮苷。2500 ~ 10000 mg/kg大鼠急性口服毒性研究表明，AFI水提取物的中位致死剂量（LD50）超过10000 mg/kg。剂量高达5000 mg/kg/天的亚急性口服毒性试验和在类似剂量范围内进行的超过13周的亚慢性毒性研究显示，没有与治疗相关的不良反应。因此，AFI水提物对大鼠的无观察不良反应水平（NOAEL）为5000 mg/kg bw/day。此外，三种遗传毒性试验（细菌反向突变、体外染色体畸变和体内微核试验）证实AFI水提取物没有遗传毒性。这些结果将为人类食用AFI水提取物的毒性风险评估提供依据。

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引用次数: 0

A CDER perspective: Landscape of New Approach Methodologies (NAMs) submitted in drug development programs CDER视角：新方法方法论（NAMs）在药物开发项目中的应用前景。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-12-06 DOI: 10.1016/j.yrtph.2025.106007

Tyna Dao, Nakissa Sadrieh

This study analyzes the landscape of studies using New Approach Methodologies (NAMs) and submitted to the FDA over the past 15 years. The study utilized a custom-developed Center for Drug Evaluation and Research (CDER) search tool to examine keywords in Module 4 of the Electronic Common Technical Document (eCTD) across various drug applications. The investigation focused on five NAM categories, including some of those identified in the 2022 Food and Drug Omnibus Reform Act (FDORA): in vitro, in silico, in chemico, nonhuman in vivo, and other NAMs. Results indicated that 93 % of NAM submissions were concentrated in two categories: in silico (49 %) and in vitro (44 %), with other categories (including in chemico, nonhuman in vivo from phylogenetically lower species and other combined methods) demonstrating significantly lower representation. In vitro NAMs, including stem cell-derived and sandwich culture models, showed higher prevalence compared to 3D models and organ chip or MPS models. The relatively high prevalence of in silico NAMs, was due to the submission of multiple study reports per application, attributed to various metabolites and the use of different in silico platforms. In chemico and nonhuman in vivo NAMs demonstrated limited submissions, with zebrafish studies predominating in the latter category. This study highlights one of CDER's activities aimed at better understanding the current usage of NAMs in drug development, while providing evidence to support areas of focus and prioritization of resources towards the validation of NAMs with significant regulatory impact potential. Despite technical limitations in the datamining work presented here, the findings confirm that CDER has been receiving NAMs data in drug applications for a long time. Nevertheless, we acknowledge that industry submits only a fraction of their NAM data to FDA, therefore we encourage increased NAM submissions which would contribute to building scientific confidence in these methods. It is only through the availability of sufficient case studies, that CDER can move towards reaching the goals of NAMs Roadmap issued in April 2025, and ultimately phasing out animal studies when possible and feasible.

本研究分析了过去15年来使用新方法方法（NAMs）并提交给FDA的研究概况。该研究使用了一个定制的药物评估和研究中心（CDER）搜索工具来检查电子通用技术文档（eCTD）模块4中的关键词，涉及各种药物应用。调查的重点是五类不干化物质，包括《2022年食品和药物综合改革法案》（FDORA）中确定的一些：体外、硅、化学、非人类体内和其他不干化物质。结果表明，93%的不声不响提交集中在两个类别：在硅（49%）和体外（44%），与其他类别（包括在化学，非人体内从系统发育较低的物种和其他组合方法）显示显著较低的代表性。体外NAMs，包括干细胞衍生和三明治培养模型，与3D模型和器官芯片或MPS模型相比，显示出更高的患病率。计算机NAMs的相对较高的患病率是由于每个申请提交了多个研究报告，归因于各种代谢物和使用不同的计算机平台。在化学和非人类体内NAMs显示有限的提交，斑马鱼研究在后者类别中占主导地位。本研究强调了CDER的一项活动，旨在更好地了解NAMs在药物开发中的当前使用情况，同时为支持具有重大监管影响潜力的NAMs验证的重点领域和资源优先级提供证据。尽管这里提出的数据挖掘工作存在技术限制，但研究结果证实，CDER长期以来一直在药物申请中接收NAMs数据。尽管如此，我们承认工业界只向FDA提交了一小部分不运动数据，因此我们鼓励增加不运动提交，这将有助于建立对这些方法的科学信心。只有通过提供足够的案例研究，CDER才能朝着2025年4月发布的NAMs路线图的目标迈进，并最终在可能和可行的情况下逐步淘汰动物研究。

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引用次数: 0

Retraction notice to“Safety evaluation and risk assessment of the herbicide roundup and its active ingredient, glyphosate, for humans” [Regul. Toxicol. Pharm. 31 (2000) 117–165] 关于“除草剂农达及其活性成分草甘膦对人类的安全性评估和风险评估”的撤回通知[法规]。Toxicol。医药，31(2000)117-165]。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-12-05 DOI: 10.1016/j.yrtph.2025.106006

Gary M. Williams , Robert Kroes , Ian C. Munro

引用次数: 0

Current approaches to the interpretation of bioactivity data from a neural network formation assay to inform developmental neurotoxicity potential of chemical exposure 目前从神经网络形成分析中解释生物活性数据的方法，以告知化学暴露的发育神经毒性潜力。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-12-03 DOI: 10.1016/j.yrtph.2025.106008

Kelly E. Carstens, Timothy J. Shafer

The Network Formation Assay (NFA) is part of a battery of in vitro assays developed to evaluate chemicals for the potential to cause developmental neurotoxicity. This assay follows the formation of interconnected networks of rat neurons using microelectrode array recordings, deriving up to 17 different endpoints informing different aspects of network activity, bursting, and connectivity. As such, it is one of the most complex assays in the battery, and interpretation of the data from this assay can be challenging. This work provides recommendations on a fit-for-purpose approach for the interpretation of data from the NFA, including the basics of the NFA experimental design, data analysis approaches, and concentration-response modeling with the ToxCast Pipeline. This manuscript also provides a workflow for data interpretation and discusses common issues that are often confronted when evaluating the data from this assay.

网络形成试验（NFA）是一组体外试验的一部分，用于评估化学物质可能引起发育性神经毒性。该分析使用微电极阵列记录大鼠神经元相互连接网络的形成，得出多达17个不同的端点，通知网络活动，破裂和连接的不同方面。因此，它是电池中最复杂的分析之一，并且从该分析中解释数据可能具有挑战性。这项工作为解释NFA数据提供了一种适合目的的方法，包括NFA实验设计的基础知识、数据分析方法和ToxCast管道的浓度响应建模。本文还提供了数据解释的工作流程，并讨论了评估该分析数据时经常遇到的常见问题。

引用次数: 0

A physiologically based pharmacokinetic (PBPK) model to align dosimetry of the isobutyl metabolic series in rats and humans. 基于生理的药代动力学（PBPK）模型来校准大鼠和人异丁基代谢系列的剂量测定。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-12-01 Epub Date: 2025-07-26 DOI: 10.1016/j.yrtph.2025.105914

Jordan N Smith, Kimberly J Tyrrell, Karl K Weitz, Willem Faber

We developed a physiologically based pharmacokinetic (PBPK) model in rats and humans for the isobutyl metabolic series, which includes isobutyl acetate, isobutanol, isobutyraldehyde, and isobutyric acid. Given chemical similarities, we used a previously developed PBPK model for the propyl metabolic series as a framework to create the isobutyl PBPK model. To support model development, we measured in vitro metabolism of isobutyl acetate in rat and human blood and liver S9 fractions. Our findings indicated that humans exhibited faster isobutyl acetate hydrolysis in liver S9 fractions compared to rats, while hydrolysis rates in blood were similar between the two species. Experiments involving closed chamber exposures of rats to isobutyl acetate or isobutanol revealed higher isobutanol concentrations in blood compared to other isobutyl compounds. Using these data to parameterize the model, the PBPK model accurately simulated available time-course concentrations of isobutyl compounds in blood of rats and humans. The isobutyl PBPK model enables comparisons of internal dose metrics across various isobutyl compound exposures and species and allows for calculation of equivalent external exposures that result in the same dose metric. Regulators can employ this PBPK model to predict and align internal dose metrics of isobutyl compounds for risk assessment purposes.

我们针对异丁基代谢系列（包括醋酸异丁酯、异丁醇、异丁醛和异丁酸）在大鼠和人体内建立了基于生理学的药代动力学（PBPK）模型。考虑到化学相似性，我们使用先前开发的丙基代谢系列PBPK模型作为框架来创建异丁基PBPK模型。为了支持模型的建立，我们测量了大鼠和人血液和肝脏S9组分中乙酸异丁酯的体外代谢。我们的研究结果表明，与大鼠相比，人类肝脏S9组分中乙酸异丁酯的水解速度更快，而血液中的水解速率在两种物种之间相似。在封闭的室内实验中，将大鼠暴露于醋酸异丁酯或异丁醇中，结果显示，与其他异丁基化合物相比，血液中异丁醇的浓度更高。利用这些数据参数化模型，PBPK模型准确地模拟了大鼠和人血液中异丁基化合物的可用时间过程浓度。异丁基PBPK模型能够比较各种异丁基化合物暴露和种类之间的内部剂量度量，并允许计算产生相同剂量度量的等效外部暴露。监管机构可以使用该PBPK模型来预测和调整异丁基化合物的内部剂量指标，以进行风险评估。

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引用次数: 0

Regulatory safety evaluation of key lime (Citrus aurantiifolia) peel ethanol extract: Acute, 90-day repeated-dose, and genotoxicity studies 酸橙皮乙醇提取物的监管安全性评估：急性、90天重复剂量和遗传毒性研究。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-11-26 DOI: 10.1016/j.yrtph.2025.106005

Yunjin Choi , Seonghui Kim , Duhyeon Kim , Kyoung Sik Park , Mi-Young Lee , Suengmok Cho

Key lime (Citrus aurantiifolia) peel, a major by-product of juice processing, is rich in flavonoids and other bioactives. To support its safe use as a food-derived ingredient, we chemically characterized key lime peel ethanol extract (KLPE) and conducted a full toxicological evaluation under OECD Test Guidelines (No. 420, 408, 471, 473, 474) and in compliance with GLP. The program included acute oral toxicity, a 90-day repeated-dose study with a 28-day recovery, and in vitro and in vivo genotoxicity assays. KLPE caused no mortality or clinical signs, and body weight, food intake, hematology, and organ weights were comparable to controls. No histopathological lesions or genotoxic effects were observed. Both the LD₅₀ and the No Observed Adverse Effect Level (NOAEL) exceeded 2000 mg/kg BW/day, the highest dose tested, indicating a wide safety margin. These results provide regulatory-grade evidence confirming the safety of KLPE for human consumption and support its application as a functional food and nutraceutical ingredient in global markets.

酸橙皮是果汁加工的主要副产品，富含黄酮类化合物和其他生物活性物质。为了支持其作为食品衍生成分的安全使用，我们对关键酸橙皮乙醇提取物（KLPE）进行了化学表征，并根据经合组织指南（TG 420, 408, 4771, 4773, 474）进行了全面的毒理学评估，并符合GLP。该计划包括急性口服毒性，90天重复剂量研究，28天恢复期，体外和体内遗传毒性测定。KLPE未引起死亡或临床症状，体重、食物摄入、血液学和器官重量与对照组相当。未观察到组织病理学病变或基因毒性作用。LD50和未观察到的不良反应水平（NOAEL）均超过2000mg /kg体重/天，这是测试的最高剂量，表明安全范围很广。这些结果提供了监管级别的证据，证实了KLPE对人类消费的安全性，并支持其作为功能性食品和营养保健成分在全球市场上的应用。

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引用次数: 0

Exploration of virtual control groups and Bayesian approaches for rat fertility studies 探索虚拟控制组和贝叶斯方法的大鼠生育研究

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-11-26 DOI: 10.1016/j.yrtph.2025.106004

Christopher J. Bowman , Dingzhou Li , Thi Dong Binh Tran , Natasha R. Catlin , Christine M. Stethem , William S. Nowland , Sarah N. Campion

This study evaluates the potential of using historical control data (HCD) in rat fertility studies to replace/reduce concurrent control animal use and improve statistical analysis. This analysis was conducted using data sourced from a single test facility using consistent animal attributes and study procedures and consisted of 13 datasets from 12 rat fertility studies conducted between 2018 and 2023. For required fertility endpoints, we have evaluated full and hybrid Virtual Control Group (VCG) and Bayesian statistical approaches compared with standard statistics used for concurrent control groups (CCG). Our findings demonstrate that the sensitivity and specificity of most required fertility endpoints were generally similar between CCG and full or hybrid VCGs of sufficient sample size. Bayesian analyses leveraging all available HCD offered similar or superior sensitivity and specificity to CCGs and VCGs (full or hybrid) for all required fertility endpoints, with some exceptions. A retrospective case study implementing these approaches with HCD illustrated similar statistical performance across all approaches in addition to the benefit of reduced animal use. Overall, this effort illustrates the potential to improve sensitivity and reduce animal use with VCG (full or hybrid) or Bayesian approaches for required fertility endpoints in the rat.

本研究评估了在大鼠生育研究中使用历史对照数据（HCD）来替代/减少同时使用对照动物和改进统计分析的潜力。该分析使用来自单一测试设施的数据进行，使用一致的动物属性和研究程序，包括2018年至2023年期间进行的12项大鼠生育研究的13个数据集。对于所需的生育终点，我们评估了完全和混合虚拟对照组（VCG）和贝叶斯统计方法，并将其与用于并发对照组（CCG）的标准统计方法进行了比较。我们的研究结果表明，大多数所需生育终点的敏感性和特异性在CCG和足够样本量的完整或杂交vcg之间大致相似。利用所有可用的HCD进行贝叶斯分析，除了一些例外，在所有所需的生育终点上，ccg和vcg（全或杂交）的敏感性和特异性与ccg相似或更高。一项使用HCD实施这些方法的回顾性案例研究表明，除了减少动物使用的好处外，所有方法的统计性能都相似。总的来说，这一努力说明了在大鼠所需的生育终点上，使用VCG（完全或混合）或贝叶斯方法提高敏感性和减少动物使用的潜力。

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引用次数: 0

An evaluation of the utility of blood concentration of somatic mutagens to inform germ cell mutagenic hazard 评价血液中体细胞诱变剂浓度对生殖细胞诱变危害的影响。

IF 3.5 4区医学 Q1 MEDICINE, LEGAL

Regulatory Toxicology and Pharmacology

Pub Date : 2025-11-22 DOI: 10.1016/j.yrtph.2025.105989

Roger Godschalk , Bente Brauwers , Connie L. Chen , Raffaella Corvi , Kerry L. Dearfield , George R. Douglas , Naveed Honarvar , David Kirkland , Frank Le Curieux , Ann-Karin Olsen , Stefan Pfuhler , Leon F. Stankowski , Paul White , Jan van Benthem , Francesco Marchetti

The Globally Harmonized System standardizes chemical hazard communication. Within this system, germ cell mutagenicity holds unique importance due to the potential of heritable mutations. Yet, such testing is rarely performed, requiring alternative approaches to assess germ cell mutagenic potential. One strategy involves using physiological parameters to predict if somatic cell mutagens reach the gonads and induce mutations in germ cells. Therefore, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee examined whether blood concentrations of somatic cell mutagens can predict genotoxic effects in germ cells. We analyzed 11 substances with dominant lethal test data and 30 with transgenic rodent gene mutation data in male germ cells, together with blood concentrations. While significant associations were found between genotoxic outcomes in somatic tissues (e.g., micronuclei, mutation induction) and outcomes for germ cell mutagenicity, considerable variability was noted in genotoxic responses. This variability could not be explained by blood concentrations alone. Notably, blood levels of substances positive in both somatic and germ cells were similar to those that were positive for somatic cell genotoxicity and negative in germ cells. We conclude that the concentration of a somatic cell genotoxic substance in blood is insufficient to predict germ cell mutagenicity.

全球协调制度使化学品危害通报标准化。在这个系统中，生殖细胞诱变具有独特的重要性，由于潜在的遗传突变。然而，这种测试很少进行，需要替代方法来评估生殖细胞致突变的潜力。一种策略是使用生理参数来预测体细胞诱变剂是否到达性腺并诱导生殖细胞发生突变。因此，健康与环境科学研究所的遗传毒理学技术委员会研究了血液中体细胞诱变剂的浓度是否可以预测生殖细胞的遗传毒性作用。我们分析了男性生殖细胞中11种具有显性致死试验数据的物质和30种具有转基因鼠基因突变数据的物质，并分析了其血药浓度。虽然在体细胞组织的基因毒性结果（如微核、突变诱导）和生殖细胞诱变结果之间发现了显著的关联，但在基因毒性反应中发现了相当大的差异。这种差异不能仅仅用血液浓度来解释。值得注意的是，血液中体细胞和生殖细胞阳性物质的水平与体细胞遗传毒性阳性和生殖细胞阴性物质的水平相似。我们的结论是，血液中体细胞遗传毒性物质的浓度不足以预测生殖细胞的诱变性。

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引用次数: 0