Systemic Toxicity Induced by Topical Application of per- and Polyfluoroalkyl Substances (PFAS) in a Murine Model

Details

• Personal Author:
  Anderson, Stacey E. ; Baur R ; Lukomska E ; Shane HL ; Weatherly LM
• Description:
  Per- and polyfluoroalkyl substances (PFAS) are a class of over 5000 synthetic, structurally diverse chemicals incorporated into industrial and consumer products. These fluorinated chemicals are used in flame-retardant products, stain resistant textiles, water and grease repellent products, food packaging material, nonstick cookware, carpets, and firefighting foams due to their stability and resistance to degradation. Carboxylic PFAS are considered long-alkyl chain if they contain 7 or more carbons in their carbon chain and short-alkyl chain if they contain 6 or fewer. Sulfonic acid PFAS are considered short chain with 5 or fewer carbons. Due to health concerns, legacy PFAS (such as perfluorooctanoic acid (PFOA; C8) and perfluorooctane sulfate (PFOS; C8)) are being phased out. Alternative PFAS (such as heptafluorobutyric acid (PFBA; C4), perfluoropentanoic acid (PFPeA; C5), perfluorohexanoic acid (PFHxA; C6), and perfluoroheptanoic acid (PFHpA; C7)) are labeled as safer alternatives to legacy PFAS, due to their shorter half-life in animals. Despite the high potential for occupational and environmental dermal exposure, dermal exposure studies are lacking. Using a murine model, the present studies analyzed organ weight, serum chemistries, histology, immune phenotyping, and gene expression to evaluate the systemic toxicity of sub-chronic 28-day dermal PFAS (C4-C8) exposure (1.25-15% or 31.25-375 mg/kg/dose in acetone vehicle). Legacy (PFOA; C8) and alternative (C4-C7) PFAS were absorbed after dermal exposure leading to an increase in detection levels in serum and urine with all PFAS tested. Legacy and alternative PFAS also increased liver weight (% body) and induced histopathology changes in the liver and skin. Gene expression changes were observed with peroxisome proliferator-activated receptors (PPAR) isoforms in the liver and skin along with changes in genes involved in steatosis, fatty acid metabolism, necrosis, skin barrier function, and inflammation. Immune-cell phenotyping identified significant changes in multiple cell sub-populations in the skin, spleen, and skin draining lymph nodes. These findings demonstrate that both legacy and alternative PFAS are absorbed through the skin and can induce systemic changes similar to those reported for oral PFAS exposure. Similar toxicity trends were seen between legacy and alterative PFAS in the liver after dermal exposure, suggesting that chain length may not be the best predictor of toxicity. However, differences in gene expression and certain cell sub-populations were observed, suggesting different mechanisms of toxicity. These findings raise concerns of alternative PFAS being promoted as a safer option and show that further investigation into PFAS dermal exposure is needed to understand the hazards of skin exposure and help promote protective measures. [Description provided by NIOSH]
• Subjects:
  Animals Immune System Occupational Health Safety Skin Toxicology
• Keywords:
  Animal Studies Chemicals Dermal Exposures Gene Expression Immune Reaction Per- And Polyfluoroalkyl Substances PFAS Skin Exposure Synthetic Materials
• 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:
  192
• NIOSHTIC Number:
  nn:20067216
• Citation:
  Toxicologist 2023 Mar; 192(S1):261
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Manufacturing ; Public Safety
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:40b1a7fa2961053a2d13eee0bfb664cb6edb4fb9d16cde129812f6892564df1082ac38da3b623a0d83619875124d2dfd0bf738eab1a628818f59aafdbde9f4a3
• Download URL:
  https://stacks.cdc.gov/view/cdc/231343/cdc_231343_DS1.pdf
• File Type:
  [PDF - 1.11 MB ]