(UB)
Research, Innovation and Economic Development
University at Buffalo (UB)
Research, Innovation and Economic Development
Research and Education in Energy,
Environment and Water
The RENEW Institute - A Multidisciplinary Initiative

Assessment of neurotoxicity of mixtures of PFAS and other neuroactive organic pollutants through integrated in silico, in vitro cellular, and in vivo models

Funding Agency: U.S. Environmental Protection Agency

Collaborators: Diana S. Aga (PI, University at Buffalo); G. Ekin Atilla-Gokcumen (University at Buffalo); Krishna Rajan (University at Buffalo); Howard Sirotkin (Stony Brook University)

Project Description: This study will integrate in vitro and in silico high-throughput testing (HTT) with in vivo tests using the zebrafish model to evaluate the neurotoxicity of mixtures of per- and polyfluoroalkyl substances (PFAS), as well as the toxicity of PFAS mixtures with organic contaminants of emerging concern. The role of cellular transporters in the active transport of PFAS will be evaluated to study the bioactivity of PFAS and their mixtures. These approaches will assess the role of PFAS in the etiology of neurodevelopmental disorders, particularly in the development of autism spectrum disorder (ASD).

The objectives of the study are to: (1) derive information on the effects of PFAS and their mixtures on cellular key events leading to neurotoxicity; (2) develop machine learning toxicity prediction tools to map the multivariate data on the structure and/or functionality of PFAS and other organic contaminants, (3) investigate the role of cellular transporters in PFAS uptake and localization, and (4) validate results from in vitro and in silico approaches using zebrafish model to assess impacts of PFAS on neurodevelopment, and on the development of complex behaviors.

We hypothesize that transporters facilitate PFAS uptake, and that exposure to mixtures of PFAS during embryogenesis disrupts brain development and contributes to the etiology of ASD and related neurodevelopmental disorders. We also hypothesize that although individual components may be too low to cause any effect at environmentally realistic concentrations, mixtures of PFAS will act in a concentration-additive manner, such that PFAS mixtures are likely to be active.

Recent Related Publications:

  1. Fong, A.; McPherson, A.; Rossi, M.; *Rajan, K.Building a roadmap for safer and sustainable material chemistries: Addressing the PFAS problem through informatics and data-driven chemistry. MRS Energy & Sustainability. 2025.12:112-120.
  2. Running, L.; Cristobal, J.R.; Karageorgiou, C; Camdzic, M.; Aguilar, J.M.N.; Gokcumen, O.; Aga, D.S.; *Atilla-Gokcumen, G. E. Investigating the Mechanism of Neurotoxic Effects of PFAS in Differentiated Neuronal Cells through Transcriptomics and Lipidomics Analysis. ACS Chemical Neuroscience. 2024.15(24):4568-4579.
  3. Ríos-Bonilla, K.M.; Aga, D.S.; Lee, J.; König, M.; Qin, W.; Cristobal, J.R.; Atilla-Gokcumen, G.E.; *Escher, B.I. Neurotoxic effects of mixtures of perfluoroalkyl substances (PFAS) at environmental and human blood concentrations. Environmental Science & Technology. 2024. 58(38):16774-84.
  4. Su, A.; Cheng, Y.; Zhang, C.; Yang, Y; She, Y.; *Rajan, K. An artificial intelligence platform for automated PFAS subgroup classification: A discovery tool for PFAS screening. Science of Total Environment. 2024. 921:171229.
  5. Zoodsma, J.; Boonkanon, C.; Running, L.; Basharat, R.; Atilla-Gokcumen, G.E., Aga, D.S.; *Sirotkin, H. Perfluorooctane Sulfonate (PFOS) Negatively Impacts Prey Capture Capabilities in Larval Zebrafish. Environmental Toxicology and Chemistry. 2024. 43(4):847-855.