PUBLICATION
Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization
- Authors
- Rivera, B.N., Ghetu, C.C., Chang, Y., Truong, L., Tanguay, R.L., Anderson, K.A., Tilton, S.C.
- ID
- ZDB-PUB-221115-12
- Date
- 2022
- Source
- Toxics 10(11): (Journal)
- Registered Authors
- Tanguay, Robyn L.
- Keywords
- chemical prioritization, mixtures, mixtures safety assessment, polycyclic aromatic hydrocarbons, sufficiently similar mixtures
- MeSH Terms
- none
- PubMed
- 36355943 Full text @ Toxics
Citation
Rivera, B.N., Ghetu, C.C., Chang, Y., Truong, L., Tanguay, R.L., Anderson, K.A., Tilton, S.C. (2022) Leveraging Multiple Data Streams for Prioritization of Mixtures for Hazard Characterization. Toxics. 10(11):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping