Immunotoxicity of PFCs (Perfluoroalkyl Compounds) Found in Fire-Fighting Foams

Details

• Personal Author:
  Maier A ; Pecquet A ; Yadav J
• Description:
  The overall objective of this project is to investigate the immunotoxicity from perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in highly exposed occupational populations. PFOA and PFOS are used in fire-fighting foams, and exposures of fire fighters occur during foam application, or from the burning and breakdown of various consumer products that contain PFOA/PFOS during a fire. Fire fighters have high body burdens of PFOA and PFOS in the serum, alongside other occupations such as PFC manufacturing. Increased risk estimates were found in firefighters for the immune-cell related cancers multiple myeloma and non-Hodgkin lymphoma. PFOA and PFOS are "presumed to be an immune hazard to humans" by the National Toxicology Program based on multiple alterations to the immune system in both experimental animals and humans. Mechanisms related to PFOS-induced cytokine inhibition were related to disruption of cell signaling (NF-kB) activation pathways. PFOA induced aspects of cellular immune responses related to inflammatory pathways (IL-1B, NF-kB, MyD88), which have been implemented in disease development. However, these responses were conflicted in the literature, suggesting further research is needed to identify the impacts of pathway perturbation at doses relevant to human exposures. The complexities of dose- response behavior may reflect competing roles of different regulators of receptor pathways, as shown for estrogenic chemicals. A potential modifier of this response could be through receptor activation (peroxisome proliferator-activated receptor - PPAR), as PFOA and PFOS are known PPAR ligands and modulate inflammatory immune pathways. We hypothesize that competing pathways are modulating the initial innate inflammatory response from PFOA/PFOS exposure in a dose- and chemical-dependent manner. The role of each pathway in modulating the innate immune response will be tested and dose-response data will be generated in two specific aims: 1. Expose human cell lines to PFOA and PFOS at a range of doses of human-relevance and identify significant alterations in pro-inflammatory gene expression (IL-1B, NF-kB, MyD88), including the role of PPAR in modulating the immune response. 2. In cells exposed as part of Aim 1, we will investigate PFOA- and PFOS-induced global gene perturbation using RNASeq and identify any novel immune-gene pathways that are altered from exposure. [Description provided by NIOSH]
• Subjects:
  Fires Immune System Occupational Health Safety
• Keywords:
  Cell Signaling Dose Response Exposure Assessment Fire Fighting Fire Retardants Immune Reaction Immunotoxins
• Publisher:
  University of Cincinnati
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Ohio ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1
• NIOSHTIC Number:
  nn:20054922
• Citation:
  18th Annual Pilot Research Project Symposium, University of Cincinnati Education and Research Center, October 5-6, 2017, Cincinnati, Ohio. Cincinnati, OH: University of Cincinnati, 2017 Oct; :1
• Email:
  Alison.Pecquet@uc.edu
• CAS Registry Number:
  Perfluorooctanesulfonic acid (CAS RN 1763-23-1) ; Perfluorooctanoic acid (CAS RN 335-67-1)
• Federal Fiscal Year:
  2018
• Performing Organization:
  University of Cincinnati
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  18th Annual Pilot Research Project Symposium, University of Cincinnati Education and Research Center, October 5-6, 2017, Cincinnati, Ohio
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7a8d271e2f57b0d2695d7efffb684221f7a4ed939dbf96995c77d0eb7eca990f1fec15228f0cc1fa038059bd1ad230b00c4473399fed26870f6745f8fe314162
• Download URL:
  https://stacks.cdc.gov/view/cdc/217332/cdc_217332_DS1.pdf
• File Type:
  [PDF - 123.80 KB ]