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Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization

There is a growing need to establish alternative approaches for mixture safety assessment of polycyclic aromatic hydrocarbons (PAHs). Due to limitations with current component-based approaches, and the lack of established methods for using whole mixtures, a promising alternative is to use sufficient...

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Autores principales: Rivera, Brianna N., Ghetu, Christine C., Chang, Yvonne, Truong, Lisa, Tanguay, Robyn L., Anderson, Kim A., Tilton, Susan C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699527/
https://www.ncbi.nlm.nih.gov/pubmed/36355943
http://dx.doi.org/10.3390/toxics10110651
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author Rivera, Brianna N.
Ghetu, Christine C.
Chang, Yvonne
Truong, Lisa
Tanguay, Robyn L.
Anderson, Kim A.
Tilton, Susan C.
author_facet Rivera, Brianna N.
Ghetu, Christine C.
Chang, Yvonne
Truong, Lisa
Tanguay, Robyn L.
Anderson, Kim A.
Tilton, Susan C.
author_sort Rivera, Brianna N.
collection PubMed
description There is a growing need to establish alternative approaches for mixture safety assessment of polycyclic aromatic hydrocarbons (PAHs). Due to limitations with current component-based approaches, and the lack of established methods for using whole mixtures, a promising alternative is to use sufficiently similar mixtures; although, an established framework is lacking. In this study, several approaches are explored to form sufficiently similar mixtures. Multiple data streams including environmental concentrations and empirically and predicted toxicity data for cancer and non-cancer endpoints were used to prioritize chemical components for mixture formations. Air samplers were analyzed for unsubstituted and alkylated PAHs. A synthetic mixture of identified PAHs was created (Creosote-Fire Mix). Existing toxicity values and chemical concentrations were incorporated to identify hazardous components in the Creosote-Fire Mix. Sufficiently similar mixtures of the Creosote-Fire Mix were formed based on (1) relative abundance; (2) toxicity values; and (3) a combination approach incorporating toxicity and abundance. Hazard characterization of these mixtures was performed using high-throughput screening in primary normal human bronchial epithelium (NHBE) and zebrafish. Differences in chemical composition and potency were observed between mixture formation approaches. The toxicity-based approach (Tox Mix) was the most potent mixture in both models. The combination approach (Weighted-Tox Mix) was determined to be the ideal approach due its ability to prioritize chemicals with high exposure and hazard potential.
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spelling pubmed-96995272022-11-26 Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization Rivera, Brianna N. Ghetu, Christine C. Chang, Yvonne Truong, Lisa Tanguay, Robyn L. Anderson, Kim A. Tilton, Susan C. Toxics Article There is a growing need to establish alternative approaches for mixture safety assessment of polycyclic aromatic hydrocarbons (PAHs). Due to limitations with current component-based approaches, and the lack of established methods for using whole mixtures, a promising alternative is to use sufficiently similar mixtures; although, an established framework is lacking. In this study, several approaches are explored to form sufficiently similar mixtures. Multiple data streams including environmental concentrations and empirically and predicted toxicity data for cancer and non-cancer endpoints were used to prioritize chemical components for mixture formations. Air samplers were analyzed for unsubstituted and alkylated PAHs. A synthetic mixture of identified PAHs was created (Creosote-Fire Mix). Existing toxicity values and chemical concentrations were incorporated to identify hazardous components in the Creosote-Fire Mix. Sufficiently similar mixtures of the Creosote-Fire Mix were formed based on (1) relative abundance; (2) toxicity values; and (3) a combination approach incorporating toxicity and abundance. Hazard characterization of these mixtures was performed using high-throughput screening in primary normal human bronchial epithelium (NHBE) and zebrafish. Differences in chemical composition and potency were observed between mixture formation approaches. The toxicity-based approach (Tox Mix) was the most potent mixture in both models. The combination approach (Weighted-Tox Mix) was determined to be the ideal approach due its ability to prioritize chemicals with high exposure and hazard potential. MDPI 2022-10-29 /pmc/articles/PMC9699527/ /pubmed/36355943 http://dx.doi.org/10.3390/toxics10110651 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rivera, Brianna N.
Ghetu, Christine C.
Chang, Yvonne
Truong, Lisa
Tanguay, Robyn L.
Anderson, Kim A.
Tilton, Susan C.
Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization
title Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization
title_full Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization
title_fullStr Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization
title_full_unstemmed Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization
title_short Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization
title_sort leveraging multiple data streams for prioritization of mixtures for hazard characterization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699527/
https://www.ncbi.nlm.nih.gov/pubmed/36355943
http://dx.doi.org/10.3390/toxics10110651
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