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The importance of variations in in vitro dosimetry to support risk assessment of inhaled toxicants
ALTEX, Volume: 41, Issue: 1
Swansea University Author:
Martin Clift
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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...
| Published in: | ALTEX |
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| ISSN: | 1868-596X |
| Published: |
ALTEX Edition
2024
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa65429 |
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| 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 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. |
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| Keywords: |
In Vitro; Toxicology; Inhalation; Lung; Risk Assessment |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
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. |
| Issue: |
1 |