Toxicological inhalation studies in rats to substantiate grouping of zinc oxide nanoforms.

IF 7.2 1区医学 Q1 TOXICOLOGY

Particle and Fibre Toxicology Pub Date : 2024-05-17 DOI:10.1186/s12989-024-00572-y

Tizia Thoma, Lan Ma-Hock, Steffen Schneider, Naveed Honarvar, Silke Treumann, Sibylle Groeters, Volker Strauss, Heike Marxfeld, Dorothee Funk-Weyer, Svenja Seiffert, Wendel Wohlleben, Martina Dammann, Karin Wiench, Noömi Lombaert, Christine Spirlet, Marie Vasquez, Nicole Dewhurst, Robert Landsiedel

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引用次数: 0

Abstract

Background: Significant variations exist in the forms of ZnO, making it impossible to test all forms in in vivo inhalation studies. Hence, grouping and read-across is a common approach under REACH to evaluate the toxicological profile of familiar substances. The objective of this paper is to investigate the potential role of dissolution, size, or coating in grouping ZnO (nano)forms for the purpose of hazard assessment. We performed a 90-day inhalation study (OECD test guideline no. (TG) 413) in rats combined with a reproduction/developmental (neuro)toxicity screening test (TG 421/424/426) with coated and uncoated ZnO nanoforms in comparison with microscale ZnO particles and soluble zinc sulfate. In addition, genotoxicity in the nasal cavity, lungs, liver, and bone marrow was examined via comet assay (TG 489) after 14-day inhalation exposure.

Results: ZnO nanoparticles caused local toxicity in the respiratory tract. Systemic effects that were not related to the local irritation were not observed. There was no indication of impaired fertility, developmental toxicity, or developmental neurotoxicity. No indication for genotoxicity of any of the test substances was observed. Local effects were similar across the different ZnO test substances and were reversible after the end of the exposure.

Conclusion: With exception of local toxicity, this study could not confirm the occasional findings in some of the previous studies regarding the above-mentioned toxicological endpoints. The two representative ZnO nanoforms and the microscale particles showed similar local effects. The ZnO nanoforms most likely exhibit their effects by zinc ions as no particles could be detected after the end of the exposure, and exposure to rapidly soluble zinc sulfate had similar effects. Obviously, material differences between the ZnO particles do not substantially alter their toxicokinetics and toxicodynamics. The grouping of ZnO nanoforms into a set of similar nanoforms is justified by these observations.

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对大鼠进行毒理学吸入研究，以证实纳米氧化锌的分组。

背景：氧化锌的形态存在很大差异，因此不可能在体内吸入研究中测试所有形态的氧化锌。因此，根据 REACH 法规，分组和交叉阅读是评估熟悉物质毒理学特征的常用方法。本文旨在研究溶解度、尺寸或涂层在以危害评估为目的的氧化锌（纳米）形式分组中的潜在作用。我们对大鼠进行了为期 90 天的吸入研究（经合组织测试准则第 (TG) 413 号），并结合生殖/发育（神经）毒性筛选测试（TG 421/424/426），对有涂层和无涂层的氧化锌纳米形态与微尺度氧化锌颗粒和可溶性硫酸锌进行了比较。此外，还通过彗星试验（TG 489）检测了吸入 14 天后鼻腔、肺部、肝脏和骨髓的遗传毒性：结果：氧化锌纳米颗粒会对呼吸道造成局部毒性。未观察到与局部刺激无关的全身影响。未发现生育能力受损、发育毒性或发育神经毒性的迹象。未发现任何测试物质具有遗传毒性。不同的氧化锌测试物质对局部的影响相似，并且在接触结束后是可逆的：除局部毒性外，本研究无法证实之前一些研究在上述毒理学终点方面的偶然发现。两种具有代表性的氧化锌纳米形态和微尺度颗粒显示出相似的局部效应。氧化锌纳米形式最有可能是通过锌离子产生影响，因为在接触结束后检测不到颗粒，而接触速溶硫酸锌也会产生类似的影响。显然，氧化锌颗粒之间的材料差异不会对其毒物动力学和毒效学产生重大影响。根据这些观察结果，将氧化锌纳米形式归为一组相似的纳米形式是合理的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Particle and Fibre Toxicology TOXICOLOGY-

CiteScore

15.90

自引率

4.00%

发文量

审稿时长

6 months

期刊介绍： Particle and Fibre Toxicology is an online journal that is open access and peer-reviewed. It covers a range of disciplines such as material science, biomaterials, and nanomedicine, focusing on the toxicological effects of particles and fibres. The journal serves as a platform for scientific debate and communication among toxicologists and scientists from different fields who work with particle and fibre materials. The main objective of the journal is to deepen our understanding of the physico-chemical properties of particles, their potential for human exposure, and the resulting biological effects. It also addresses regulatory issues related to particle exposure in workplaces and the general environment. Moreover, the journal recognizes that there are various situations where particles can pose a toxicological threat, such as the use of old materials in new applications or the introduction of new materials altogether. By encompassing all these disciplines, Particle and Fibre Toxicology provides a comprehensive source for research in this field.