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HERO ID
5080589
Reference Type
Journal Article
Title
Perfluorohexanoic acid toxicity, part I: Development of a chronic human health toxicity value for use in risk assessment
Author(s)
Luz, AL; Anderson, JK; Goodrum, P; Durda, J
Year
2019
Is Peer Reviewed?
1
Journal
Regulatory Toxicology and Pharmacology
ISSN:
0273-2300
EISSN:
1096-0295
Publisher
Academic Press Inc.
Volume
103
Page Numbers
41-55
Language
English
PMID
30639337
DOI
10.1016/j.yrtph.2019.01.019
Web of Science Id
WOS:000476683100005
Abstract
Perfluorohexanoic acid (PFHxA) is a short-chain, six-carbon perfluoroalkyl acid (PFAA) and is a primary impurity, degradant, and metabolite associated with the short-chain fluorotelomer-based chemistry used globally today. The transition to short-chain fluorotelomer-based products as a cornerstone in replacement fluorochemistry has raised questions regarding potential human health risks associated with exposure to fluorotelomer-based substances and therefore, PFHxA. Here, we present a critical review of data relevant to such a risk assessment, including epidemiological studies and in vivo and in vitro toxicity studies that examined PFHxA acute, subchronic, and chronic toxicity. Key findings from toxicokinetic and mode-of-action studies are also evaluated. Sufficient data exist to conclude that PFHxA is not carcinogenic, is not a selective reproductive or developmental toxicant, and does not disrupt endocrine activity. Collectively, effects caused by PFHxA exposure are largely limited to potential kidney effects, are mild and/or reversible, and occur at much higher doses than observed for perfluorooctanoic acid (PFOA). A chronic human-health-based oral reference dose (RfD) for PFHxA of 0.25 mg/kg-day was calculated using benchmark dose modeling of renal papillary necrosis from a chronic rat bioassay. This RfD is four orders of magnitude greater than the chronic oral RfD calculated by the U.S. Environmental Protection Agency for PFOA. The PFHxA RfD can be used to inform public health decisions related to PFHxA and fluorotelomer precursors for which PFHxA is a terminal degradant. These findings clearly demonstrate that PFHxA is less hazardous to human health than PFOA. The analyses presented support site-specific risk assessments as well as product stewardship initiatives for current and future short-chain fluorotelomer-based products.
Keywords
PFHxA; Perfluorohexanoic acid; Fluorotelomers; Human health; Benchmark dose; Oral reference dose
Tags
PFAS
•
Additional PFAS (formerly XAgency)
•
Expanded PFAS SEM (formerly PFAS 430)
Litsearch: September 2019
PubMed
Not prioritized for screening
Potassium perfluorooctanoate
Sodium perfluorooctanoate
•
PFAS 150
Literature Search Update December 2020
PubMed
WOS
Literature Search August 2019
PubMed
Web of Science
Not prioritized for screening
Ammonium perfluorooctanoate
Perfluorohexanoic acid
Perfluorooctanoic acid
1,1,1,3,3,3-Hexafluoro-2- (fluoromethoxy)propane
•
PFBA
Supplemental References
•
PFHxA
LitSearch Update: Feb 2018 - May 2019
PubMed
ToxNet
Literature Search
Pubmed
Toxnet
LitSearch Update: May 2019 - May 2020
WoS
Scopus: April 2021
Title and Abstract Screening
Tagged as Supplemental
ADME TK
HAWC
•
PFNA
•
PFOA (335-67-1) and PFOS (1763-23-1)
Literature Search Update (2013-2019)
PubMed
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