Systemic and Immunotoxicity Induced by Topical Application of Perfluorohexane Sulfonic Acid (PFHxS) in a Murine Model

Details

• Personal Author:
  Anderson, Stacey E. ; Cooper MP ; Jackson LG ; Lukomska E ; Shane HL ; Weatherly LM
• Description:
  Background and Purpose: Per- and polyfluoroalkyl substances (PFAS) are a large group (over 12,000) of synthetic surfactants with unique chemical and physical properties including water and oil resistance and heat and corrosion stability. Due to these properties, PFAS are incorporated into the manufacturing of both consumer and industrial products including food packaging, textile coatings, fire-retardant foams, firefighter personal protective equipment, cleaners, wood glue, ski wax, leather, nonstick cookware, carpets, and construction material and more recent studies have found applications of PFAS to include cosmetics, personal care products, hand sanitizers, and makeup removers. However, these properties due to their strong carbon-fluorine bond, make these chemicals resistant to degradation and allow them to accumulate in the environment and in humans, leading to environmental and human health concerns. Perfluorohexane sulfonic acid (PFHxS) is a 6-carbon chain PFAS with a long half-life (4.7-35 years in humans) that has been detected in human samples. Despite the high potential for occupational and environmental dermal exposure, dermal exposure studies are lacking. To help fill in this knowledge gap, the present study aims to investigate systemic effects of dermal exposure of PFHxS in a murine model. Methods: The present study analyzed organ weight, serum chemistries, histology, immune phenotyping, gene expression, and spleen and serum IgM response to sheep red blood cells (SRBC) to evaluate the systemic and immunotoxicity of sub-chronic 28- or 10-day dermal exposure of PFHxS (0.625-5% or 15.63-125 mg/kg/dose). Results: Elevated levels of PFHxS were detected in the serum and urine, suggesting that absorption is occurring through the dermal route. Liver weight (% body) significantly increased and spleen weight (% body) significantly decreased with PFHxS exposure, which was supported by histopathological changes. Additionally, PFHxS significantly reduced the humoral immune response and altered immune subsets in the spleen, suggesting immunosuppression. Gene expression changes were observed in the liver, skin, and spleen with genes involved in fatty acid metabolism, necrosis, and inflammation. Immune-cell phenotyping identified significant decreases in B-cells, NK cells, and CD11b+ cells in the spleen along with increases in CD4+ and CD8+ T-cells, NK cells, and neutrophils in the skin. Conclusions: These findings support dermal PFHxS-induced liver damage and immune suppression similar to those reported for oral PFAS exposure. Unique mechanisms of toxicity are suggested between PFHxS and other PFAS previously studied. Further investigation into PFAS dermal exposure is needed to understand the hazards of skin exposure on systemic toxicity and immune function. Overall, this data raises concern about PFAS dermal exposure and suggest the need for further examination. [Description provided by NIOSH]
• Subjects:
  Immune System Laboratories Occupational Health Safety Skin
• Keywords:
  Dermal Exposures Gene Expression Histopathology Immune Reaction Laboratory Animals Liver Damage Per- And Polyfluoroalkyl Substances PFAS
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  198
• NIOSHTIC Number:
  nn:20069330
• Citation:
  Toxicologist 2024 Mar; 198(S1):278
• CAS Registry Number:
  Perfluorohexanesulfonic acid (CAS RN 355-46-4)
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Manufacturing ; Public Safety
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 63rd Annual Meeting & ToxExpo, March 10-14, 2024, Salt Lake City, Utah
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dfdd32d85a31ef9a5ff4d63c595c06bc1e756e365fa5171169679f449b910e4ebdb58e794c21f51bd62877ca607f591da472599d12fa51a7966e9a25fbced18
• Download URL:
  https://stacks.cdc.gov/view/cdc/207830/cdc_207830_DS1.pdf
• File Type:
  [PDF - 558.88 KB ]