Linking PAH Exposure to Health Outcomes Using a Primary Human In - - PowerPoint PPT Presentation

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Linking PAH Exposure to Health Outcomes Using a Primary Human In - - PowerPoint PPT Presentation

Oct 03, 2023 390 likes •464 views

Linking PAH Exposure to Health Outcomes Using a Primary Human In Vitro Respiratory Model Susan C. Tilton Project Lead Team D. Williams W. Altemeier S. Randell Y. Tesfaigzi Linking PAH Exposure to Health Outcomes Using a Primary Human In

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SLIDE 1

Linking PAH Exposure to Health Outcomes Using a Primary Human In Vitro Respiratory Model

Team

  • D. Williams
  • W. Altemeier
  • S. Randell
  • Y. Tesfaigzi

Susan C. Tilton

Project Lead

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Linking PAH Exposure to Health Outcomes Using a Primary Human In Vitro Respiratory Model

Overall objective: To understand how PAHs contribute to toxicity in mixtures and establish a relationship between chemical exposure and toxicity in a human lung model.

  • Quantify the toxicity of individual PAHs and

PAH mixtures in the 3D human lung model.

  • Assess the role of metabolism on the

toxicity of individual PAHs

  • Elucidate the mechanisms of PAH toxicity

in the 3D human lung model.

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SLIDE 3

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Assessing Toxicity of PAHs and Mixtures

Goals:

  • Assess the toxicity of diverse PAHs and

mixtures using benchmark dose modeling and threshold dose analyses.

  • Determine whether individual PAHs

contribute to the toxicity of PAH mixtures in an additive manner.

  • Determine whether remediation reduces

the threat that PAHs and complex PAH environmental mixtures pose to human health.

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SLIDE 4

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Developing sufficiently similar mixtures for testing

  • Comparison of mixture formations from

legacy creosote site sampling formed at environmentally relevant ratios

  • Determine whether individual PAHs

contribute to toxicity in additive manner

Abundance Mixture (14-100 uM) Toxicity Mixture (10-600 uM)

CYP1A1

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SLIDE 5

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Assessing Toxicity of PAHs and Mixtures

  • Identify gene and metabolite

signatures linked to toxicity.

  • Model signatures predictive of cancer

risk

  • Assess mechanisms of chemical

toxicity

  • Evaluate contributors to disease

susceptibility

Enriched Pathways

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SLIDE 6

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Assess the role of metabolism on PAH toxicity in the 3D human lung model

Goals:

  • Measure uptake and

metabolism of biologically active PAHs in 3D human lung model.

  • Determine how gene-

environment interactions influence the toxicity of PAHs in the 3D human lung model.

  • Assess human health

hazards associated with environmental PAH exposures measured at Superfund sites.

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SLIDE 7

Thank you

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More Information: https://superfund.oregonstate.edu/

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