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The Short-Term Inhalation Study (STIS) as a Range Finder and Screening Tool in a Tiered Grouping Strategy

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In Vivo Inhalation Toxicity Screening Methods for Manufactured Nanomaterials

Abstract

The rat short-term inhalation study (STIS; 5 days exposure, 6 h/day; approx. 3-week postexposure observation) allows assessing test material-induced early respiratory tract effects, the progression or reversibility of effects, pulmonary particle deposition, and potential test material translocation to extra-pulmonary tissues and the evolvement of systemic effects. This chapter provides details on the STIS study design focusing on aerosol characterization, performance of bronchoalveolar lavage in half a lung and preparation of the other half for histopathology. Five case studies (CSs) exemplify how the rat STIS can be used for initial safety assessments, e.g., within the previously published Decision-making framework for the grouping and testing of nanomaterials. This tiered framework allows grouping nanomaterials as soluble (CS 1: CuO, ZnO); high aspect ratio nanomaterials (CS 2: multiwall carbon nanotubes); passive (CS 3: BaSO4, ZrO2, graphite nanoplatelets); or active (CS 4: CeO2, TiO2). CS 5 addresses different amorphous SiO2 that are either soluble, passive, or active. In conclusion, the rat STIS and 28-day/90-day inhalation toxicity studies reveal comparable effects, and the rankings of no-observed adverse effect concentrations are very similar. Compared with 28-day and 90-day inhalation toxicity studies (OECD Test Guidelines 412 and 413), the rat STIS requires fewer animals and its duration is considerably shorter. Thereby, this test serves the 3Rs principle to replace, reduce, and refine animal testing. If 28-day and 90-day inhalation toxicity studies are mandatory for regulatory purposes, the rat STIS is a suitable range-finding study to select appropriate concentrations for the longer-term studies.

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Acknowledgements

Dr. med. vet. Ursula G. Sauer (Scientific Consultancy—Animal Welfare, Germany) was hired as scientific writer of this chapter.

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Authors and Affiliations

  1. Product Safety, BASF SE, Ludwigshafen, Germany

    Karin Wiench

  2. Experimental Toxicology and Ecology, BASF SE, Ludwigshafen, Germany

    Lan Ma-Hock

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  1. Karin Wiench
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Correspondence to Karin Wiench .

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Editors and Affiliations

  1. Graduate School of Health Management, Keio University, Fujisawa, Kanagawa, Japan

    Toru Takebayashi

  2. Experimental Toxicology and Ecology, BASF SE, Ludwigshafen am Rhein, Germany

    Robert Landsiedel

  3. National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan

    Masashi Gamo

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Wiench, K., Ma-Hock, L. (2019). The Short-Term Inhalation Study (STIS) as a Range Finder and Screening Tool in a Tiered Grouping Strategy. In: Takebayashi, T., Landsiedel, R., Gamo, M. (eds) In Vivo Inhalation Toxicity Screening Methods for Manufactured Nanomaterials. Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-13-8433-2_2

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