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3455968 
Journal Article 
Review 
Is there a human health risk associated with indirect exposure to perfluoroalkyl carboxylates (PFCAs)? 
Rand, AA; Mabury, SA 
2017 
Yes 
Toxicology
ISSN: 0300-483X
EISSN: 1879-3185 
375 
28-36 
English 
The production and widespread use of poly- and perfluoroalkyl substances (PFAS) has led to their presence in the environment, wildlife, and humans. Particularly, the perfluoroalkyl carboxylates (PFCAs) are pervasive throughout the world and have been found at ng/mL concentrations in human blood. PFCAs, especially those having longer carbon chain lengths (≥C6), are associated with developmental and hormonal effects, immunotoxicity, and promote tumor growth in rodents through their role as PPARα agonists. Humans are directly exposed to PFCAs primarily through contaminated food, drinking water, and house dust. However, indirect exposure to PFCAs through the biotransformation of fluorotelomer-based substances may also be a significant, yet relatively underappreciated pathway. We are exposed to fluorotelomer-based substances through use of consumer products, ingestion of food, or from inhalation of dust particles, but the risk of this exposure has been largely uncharacterized. Here, we summarize the work that has been done to characterize toxicity of the classes of fluorotelomer-based substances shown to biotransform to PFCAs: the polyfluoroalkyl phosphate esters (PAPs), fluorotelomer alcohols (FTOHs), fluorotelomer iodides (FTIs), and fluorotelomer acrylate monomers (FTAcs). These fluorotelomer-based substances biotranform to yield PFCAs, yet also form bioactive intermediate metabolites, which have been observed to be more toxic than their corresponding PFCAs. We address what is known regarding the toxicity of the fluorotelomer-based substances and their metabolites, with focus on covalent binding to biological nucleophiles, such as glutathione, proteins, and DNA, as a possible mechanism of toxicity that may influence the risk of indirect exposure to PFCAs. 
Carboxylic Acids/toxicity; Environmental Exposure/adverse effects; Fluorocarbons/toxicity; Health Status; Risk Factors; Bioactivation; Covalent binding; Exposure; Fluorotelomer-based substances; Perfluorinated carboxylates; Toxicity 
PFAS
• 6:2/8:2 diPAP
     Literature Search
          WOS
     Screening Results
          Reviews/Reg docs
• 6:2 diPAP
     Literature Search
          WOS
     Screening Results
          Reviews/Reg docs
• FtOH 6:2
     Screening Results
          Reviews/Reg docs
• ^Per- and Polyfluoroalkyl Substances (PFAS)
     PFOA (335-67-1) and PFOS (1763-23-1)
          Literature Search – Adverse outcome pathway (2015-present)
               WOS
     FtOH 6:2 (647-42-7)
          Literature Search
               WOS
     6:2 diPAP (57677-95-9)
          Literature Search
               WOS
               Additional Strategies
     6:2/8:2 diPAP (943913-15-3)
          Literature Search
               WOS
• PFNA
     Literature Search
          Exclusions
               Reviews
          Toxline
     PFNA May 2019 Update
          Toxnet
• PFOA (335-67-1) and PFOS (1763-23-1)
     Literature Search – Adverse outcome pathway (2015-present)
          WOS
     Screening Results
          Excluded/Not on Topic
     Literature Search Update (2013-2019)
          WOS