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The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants

Martin Clift Orcid Logo

ALTEX, Volume: 41, Issue: 1

Swansea University Author: Martin Clift Orcid Logo

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DOI (Published version): 10.14573/altex.2305311

Abstract

In vitro methods provide a key opportunity to model human-relevant exposure scenarios for hazardidentification of inhaled toxicants. Compared to in vivo tests, in vitro methods have the advantageof assessing effects of inhaled toxicants caused by differences in dosimetry, e.g., variations in concent...

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ISSN: 1868-596X
Published: ALTEX Edition 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa65429
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spelling v2 65429 2024-01-09 The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants 71bf49b157691e541950f5c3f49c9169 0000-0001-6133-3368 Martin Clift Martin Clift true false 2024-01-09 BMS In vitro methods provide a key opportunity to model human-relevant exposure scenarios for hazardidentification of inhaled toxicants. Compared to in vivo tests, in vitro methods have the advantageof assessing effects of inhaled toxicants caused by differences in dosimetry, e.g., variations in concentration(exposure intensity), exposure duration, and exposure frequency, in an easier way.Variations in dosimetry can be used to obtain information on adverse effects in human-relevantexposure scenarios that can be used for risk assessment. Based on the published literature ofexposure approaches using air-liquid interface models of the respiratory tract, supplemented withadditional experimental data from the EU H2020 project “PATROLS” and research funded by theDutch Ministry of Agriculture, Nature and Food Quality, the advantages and disadvantages of differentexposure methods and considerations to design an experimental setup are summarized anddiscussed. As the cell models used are models for the respiratory epithelium, our focus is on thelocal effects in the airways. In conclusion, in order to generate data from in vitro methods for riskassessment of inhaled toxicants it is recommended that (1) it is considered what information really isneeded for hazard or risk assessment; (2) the exposure system that is most suitable for the chemicalto be assessed is chosen; (3) a deposited dose that mimics deposition in the human respiratory tractis used, and (4) the post-exposure sampling methodology should be carefully considered and relevantto the testing strategy used. Journal Article ALTEX 41 1 ALTEX Edition 1868-596X In Vitro; Toxicology; Inhalation; Lung; Risk Assessment 9 1 2024 2024-01-09 10.14573/altex.2305311 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Another institution paid the OA fee This re-search was funded by the Dutch Ministry of Agriculture, Nature and Food Quality, project 10B.5.1-4. This research is part of the NWA-ORC VHP4Safety research project. The VHP4Safety re-search project is funded by the Netherlands Research Council (NWO) “Netherlands Research Agenda: Research on Routes by Consortia” (NWA-ORC 1292.19.272). B. Rothen-Rutishauser acknowledges the NRP 79 grant (Nr. 407940_206331/1) from the Swiss National Science Foundation and the Adolphe Merkle Foun-dation. The research reported in supplementary file 2 was sup-ported by EU-project PATROLS (Physiologically Anchored Tools for Realistic nanomaterial hazard aSsessment), No. 760813, and by the Dutch Ministry of Infrastructure and Water Management. 2024-03-21T12:04:36.4860478 2024-01-09T18:55:29.4549888 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Martin Clift 0000-0001-6133-3368 1 65429__29424__a81ff0f6462c4cfd988fde71d306c22a.pdf Staal et al (2024).pdf 2024-01-09T19:02:00.4563313 Output 900854 application/pdf Version of Record true © The Authors, 2023. This work is licensed under a Creative Commons Attribution 4.0 International License. true eng https://creativecommons.org/licenses/by/4.0/
title The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants
spellingShingle The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants
Martin Clift
title_short The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants
title_full The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants
title_fullStr The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants
title_full_unstemmed The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants
title_sort The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants
author_id_str_mv 71bf49b157691e541950f5c3f49c9169
author_id_fullname_str_mv 71bf49b157691e541950f5c3f49c9169_***_Martin Clift
author Martin Clift
author2 Martin Clift
format Journal article
container_title ALTEX
container_volume 41
container_issue 1
publishDate 2024
institution Swansea University
issn 1868-596X
doi_str_mv 10.14573/altex.2305311
publisher ALTEX Edition
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description In vitro methods provide a key opportunity to model human-relevant exposure scenarios for hazardidentification of inhaled toxicants. Compared to in vivo tests, in vitro methods have the advantageof assessing effects of inhaled toxicants caused by differences in dosimetry, e.g., variations in concentration(exposure intensity), exposure duration, and exposure frequency, in an easier way.Variations in dosimetry can be used to obtain information on adverse effects in human-relevantexposure scenarios that can be used for risk assessment. Based on the published literature ofexposure approaches using air-liquid interface models of the respiratory tract, supplemented withadditional experimental data from the EU H2020 project “PATROLS” and research funded by theDutch Ministry of Agriculture, Nature and Food Quality, the advantages and disadvantages of differentexposure methods and considerations to design an experimental setup are summarized anddiscussed. As the cell models used are models for the respiratory epithelium, our focus is on thelocal effects in the airways. In conclusion, in order to generate data from in vitro methods for riskassessment of inhaled toxicants it is recommended that (1) it is considered what information really isneeded for hazard or risk assessment; (2) the exposure system that is most suitable for the chemicalto be assessed is chosen; (3) a deposited dose that mimics deposition in the human respiratory tractis used, and (4) the post-exposure sampling methodology should be carefully considered and relevantto the testing strategy used.
published_date 2024-01-09T12:04:33Z
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