Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment
Abstract Background Nanomaterials can exist in different nanoforms (NFs). Their grouping may be supported by the formulation of hypotheses which can be interrogated via integrated approaches to testing and assessment (IATA). IATAs are decision trees that guide the user through tiered testing strateg...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12989-022-00508-4 |
| _version_ | 1811315592519483392 |
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| author | Luisana Di Cristo Victor C. Ude Georgia Tsiliki Giuseppina Tatulli Alessio Romaldini Fiona Murphy Wendel Wohlleben Agnes G. Oomen Pier P. Pompa Josje Arts Vicki Stone Stefania Sabella |
| author_facet | Luisana Di Cristo Victor C. Ude Georgia Tsiliki Giuseppina Tatulli Alessio Romaldini Fiona Murphy Wendel Wohlleben Agnes G. Oomen Pier P. Pompa Josje Arts Vicki Stone Stefania Sabella |
| author_sort | Luisana Di Cristo |
| collection | DOAJ |
| description | Abstract Background Nanomaterials can exist in different nanoforms (NFs). Their grouping may be supported by the formulation of hypotheses which can be interrogated via integrated approaches to testing and assessment (IATA). IATAs are decision trees that guide the user through tiered testing strategies (TTS) to collect the required evidence needed to accept or reject a grouping hypothesis. In the present paper, we investigated the applicability of IATAs for ingested NFs using a case study that includes different silicon dioxide, SiO2 NFs. Two oral grouping hypotheses addressing local and systemic toxicity were identified relevant for the grouping of these NFs and verified through the application of oral IATAs. Following different Tier 1 and/or Tier 2 in vitro methods of the TTS (i.e., in vitro dissolution, barrier integrity and inflammation assays), we generated the NF datasets. Furthermore, similarity algorithms (e.g., Bayesian method and Cluster analysis) were utilized to identify similarities among the NFs and establish a provisional group(s). The grouping based on Tier 1 and/or Tier 2 testing was analyzed in relation to available Tier 3 in vivo data in order to verify if the read-across was possible and therefore support a grouping decision. Results The measurement of the dissolution rate of the silica NFs in the oro-gastrointestinal tract and in the lysosome identified them as gradually dissolving and biopersistent NFs. For the local toxicity to intestinal epithelium (e.g. cytotoxicity, membrane integrity and inflammation), the biological results of the gastrointestinal tract models indicate that all of the silica NFs were similar with respect to the lack of local toxicity and, therefore, belong to the same group; in vivo data (although limited) confirmed the lack of local toxicity of NFs. For systemic toxicity, Tier 1 data did not identify similarity across the NFs, with results across different decision nodes being inconsistent in providing homogeneous group(s). Moreover, the available Tier 3 in vivo data were also insufficient to support decisions based upon the obtained in vitro results and relating to the toxicity of the tested NFs. Conclusions The information generated by the tested oral IATAs can be effectively used for similarity assessment to support a grouping decision upon the application of a hypothesis related to toxicity in the gastrointestinal tract. The IATAs facilitated a structured data analysis and, by means of the expert’s interpretation, supported read-across with the available in vivo data. The IATAs also supported the users in decision making, for example, reducing the testing when the grouping was well supported by the evidence and/or moving forward to advanced testing (e.g., the use of more suitable cellular models or chronic exposure) to improve the confidence level of the data and obtain more focused information. |
| first_indexed | 2024-04-13T11:33:09Z |
| format | Article |
| id | doaj.art-8231f4448c434f63ae8a90493ceb1245 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-04-13T11:33:09Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-8231f4448c434f63ae8a90493ceb12452022-12-22T02:48:31ZengBMCParticle and Fibre Toxicology1743-89772022-12-0119112610.1186/s12989-022-00508-4Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessmentLuisana Di Cristo0Victor C. Ude1Georgia Tsiliki2Giuseppina Tatulli3Alessio Romaldini4Fiona Murphy5Wendel Wohlleben6Agnes G. Oomen7Pier P. Pompa8Josje Arts9Vicki Stone10Stefania Sabella11D3 PharmaChemistry, Nanoregulatory Group, Italian Institute of TechnologyNano Safety Research Group, School of Engineering and Physical Sciences, Heriot Watt UniversityInstitute for the Management of Information Systems, Athena Research CenterNanobiointeractions & Nanodiagnostics, Istituto Italiano Di Tecnologia (IIT)D3 PharmaChemistry, Nanoregulatory Group, Italian Institute of TechnologyNano Safety Research Group, School of Engineering and Physical Sciences, Heriot Watt UniversityDepartment Material Physics and Department of Experimental Toxicology & Ecology, BASF SENational Institute for Public Health and the Environment (RIVM)Nanobiointeractions & Nanodiagnostics, Istituto Italiano Di Tecnologia (IIT)NouryonNano Safety Research Group, School of Engineering and Physical Sciences, Heriot Watt UniversityD3 PharmaChemistry, Nanoregulatory Group, Italian Institute of TechnologyAbstract Background Nanomaterials can exist in different nanoforms (NFs). Their grouping may be supported by the formulation of hypotheses which can be interrogated via integrated approaches to testing and assessment (IATA). IATAs are decision trees that guide the user through tiered testing strategies (TTS) to collect the required evidence needed to accept or reject a grouping hypothesis. In the present paper, we investigated the applicability of IATAs for ingested NFs using a case study that includes different silicon dioxide, SiO2 NFs. Two oral grouping hypotheses addressing local and systemic toxicity were identified relevant for the grouping of these NFs and verified through the application of oral IATAs. Following different Tier 1 and/or Tier 2 in vitro methods of the TTS (i.e., in vitro dissolution, barrier integrity and inflammation assays), we generated the NF datasets. Furthermore, similarity algorithms (e.g., Bayesian method and Cluster analysis) were utilized to identify similarities among the NFs and establish a provisional group(s). The grouping based on Tier 1 and/or Tier 2 testing was analyzed in relation to available Tier 3 in vivo data in order to verify if the read-across was possible and therefore support a grouping decision. Results The measurement of the dissolution rate of the silica NFs in the oro-gastrointestinal tract and in the lysosome identified them as gradually dissolving and biopersistent NFs. For the local toxicity to intestinal epithelium (e.g. cytotoxicity, membrane integrity and inflammation), the biological results of the gastrointestinal tract models indicate that all of the silica NFs were similar with respect to the lack of local toxicity and, therefore, belong to the same group; in vivo data (although limited) confirmed the lack of local toxicity of NFs. For systemic toxicity, Tier 1 data did not identify similarity across the NFs, with results across different decision nodes being inconsistent in providing homogeneous group(s). Moreover, the available Tier 3 in vivo data were also insufficient to support decisions based upon the obtained in vitro results and relating to the toxicity of the tested NFs. Conclusions The information generated by the tested oral IATAs can be effectively used for similarity assessment to support a grouping decision upon the application of a hypothesis related to toxicity in the gastrointestinal tract. The IATAs facilitated a structured data analysis and, by means of the expert’s interpretation, supported read-across with the available in vivo data. The IATAs also supported the users in decision making, for example, reducing the testing when the grouping was well supported by the evidence and/or moving forward to advanced testing (e.g., the use of more suitable cellular models or chronic exposure) to improve the confidence level of the data and obtain more focused information.https://doi.org/10.1186/s12989-022-00508-4Oral dissolutionNanoformsIngestionLocal toxicitySystemic toxicitySimilarity assessment |
| spellingShingle | Luisana Di Cristo Victor C. Ude Georgia Tsiliki Giuseppina Tatulli Alessio Romaldini Fiona Murphy Wendel Wohlleben Agnes G. Oomen Pier P. Pompa Josje Arts Vicki Stone Stefania Sabella Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment Particle and Fibre Toxicology Oral dissolution Nanoforms Ingestion Local toxicity Systemic toxicity Similarity assessment |
| title | Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment |
| title_full | Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment |
| title_fullStr | Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment |
| title_full_unstemmed | Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment |
| title_short | Grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment |
| title_sort | grouping of orally ingested silica nanomaterials via use of an integrated approach to testing and assessment to streamline risk assessment |
| topic | Oral dissolution Nanoforms Ingestion Local toxicity Systemic toxicity Similarity assessment |
| url | https://doi.org/10.1186/s12989-022-00508-4 |
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