Skip to main content
U.S. flag

An official website of the United States government

Here’s how you know

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

HTTPS

Secure .gov websites use HTTPS
A lock ( Lock A locked padlock ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

  • Environmental Topics
  • Laws & Regulations
  • Report a Violation
  • About EPA
Risk Assessment
Contact Us

Perfluorohexane Sulfonate (PFHxS) Alters the Choroid Plexus Transcriptome and Enters the Developing Rat Brain

On this page:

  • Overview
Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants associated with developmental neurotoxicity. Recently, human biomonitoring showed that PFAS are detectable in newborn cerebrospinal fluid (CSF). This suggests that these chemicals may cross the protective blood-brain and blood-CSF barriers. Thus, understanding how PFAS enter the brain is crucial for determining their risk. To confirm whether PFAS can cross the brain barriers and to delineate a potential mechanism, we exposed pregnant rats to perfluorohexane sulfonate (PFHxS, 50 mg/kg/day) or vehicle control during pregnancy and lactation. PFHxS was chosen as the test compound due to its efficacy in entering human CSF. From the day of birth until postnatal day 14 (PN14), PFHxS was measured in pup sera and in perfused brain on PN6. These data show that PFHxS has significant lactational transfer, and brain PFHxS is ~1/100 of serum. This shows that PFHxS enters the brain but likely not by passive diffusion. Next, we performed RNA-Seq of the PN6 blood-CSF barrier (choroid plexus). We detected 158 differentially expressed genes in PFHxS exposed animals compared with controls (FDR q<0.05). Pathway analyses revealed that PFHxS downregulates endoplasmic reticulum stress and alters expression of carboxylic acid transport. Together, these data suggest that PFHxS cross the brain barriers. Additionally, PFHxS is likely not diffusing into the brain, but may be transported across the brain barriers via endogenous carboxylic acid transporters. As PFHxS and many other PFAS are structurally similar to fatty acids, this mechanism may be biologically plausible. This work does not reflect US EPA policy.    

Impact/Purpose

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants associated with developmental neurotoxicity. Recently, human biomonitoring showed that PFAS are detectable in newborn cerebrospinal fluid (CSF). This suggests that these chemicals may cross the protective blood-brain and blood-CSF barriers (the "brain barriers"). In order to exert neurotoxicity many chemicals must first enter the brain, thus understanding how PFAS may cross the brain barriers is crucial for determining their risk. To confirm whether PFAS can cross the brain barriers and to delineate a potential mechanism, we exposed pregnant and lactating rats to perfluorohexane sulfonate (PFHxS) or vehicle control (water) and measured serum and brain PFHxS in their offspring. We show that PFHxS enters the developing brain, but likely not by diffusion. Next, we sequenced the blood-CSF barrier (choroid plexus of the brain) in PFHxS and control pups. We identified 158 differentially expressed genes in PFHxS pups, and many of these are related to carboxylic acid transport. As PFHxS and many other PFAS are structurally similar to fatty acids, this suggests that PFHxS may enter the developing brain by carboxylic acid transport. 

Citation

O'Shaughnessy, Katherine, A. Sasser, K. Bell, AND J. McCord. Perfluorohexane Sulfonate (PFHxS) Alters the Choroid Plexus Transcriptome and Enters the Developing Rat Brain. The Developmental Neurotoxicology Society (DNTS) Annual Meeting, Pittsburgh, PA, June 22 - 26, 2024.
  • Risk Assessment Home
  • About Risk Assessment
  • Risk Recent Additions
  • Human Health Risk Assessment
  • Ecological Risk Assessment
  • Risk Advanced Search
    • Risk Publications
  • Risk Assessment Guidance
  • Risk Tools and Databases
  • Superfund Risk Assessment
  • Where you live
Contact Us to ask a question, provide feedback, or report a problem.
Last updated on November 25, 2024
United States Environmental Protection Agency

Discover.

  • Accessibility Statement
  • Budget & Performance
  • Contracting
  • EPA www Web Snapshots
  • Grants
  • No FEAR Act Data
  • Privacy
  • Privacy and Security Notice

Connect.

  • Data
  • Inspector General
  • Jobs
  • Newsroom
  • Open Government
  • Regulations.gov
  • Subscribe
  • USA.gov
  • White House

Ask.

  • Contact EPA
  • EPA Disclaimers
  • Hotlines
  • FOIA Requests
  • Frequent Questions

Follow.