Subacute dermal toxicity of perfluoroalkyl carboxylic acids: comparison with different carbon-chain lengths in human skin equivalents and systemic effects of perfluoroheptanoic acid in Sprague Dawley rats

• Published in: Archives of toxicology 2020-02, Vol.94 (2), p.523-539
• Main Authors: Han, Ji-Seok, Jang, Sumi, Son, Hwa-Young, Kim, Yong-Bum, Kim, Younhee, Noh, Jung-Ho, Kim, Mi-Jeong, Lee, Byoung-Seok
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2'-Deoxyguanosine - metabolism; 8-Hydroxydeoxyguanosine; Abnormalities; Acids; Animals; Biocompatibility; Biomedical and Life Sciences; Biomedicine; Body Weight - drug effects; Carboxylic acids; Carboxylic Acids - chemistry; Carboxylic Acids - toxicity; Cell Culture Techniques; Cell viability; Chains; Consumer products; Degeneration; Dermal absorption; Dermatitis; Dose-Response Relationship, Drug; Environmental Health; Equivalence; Exposure; Female; Fluorocarbons - chemistry; Fluorocarbons - toxicity; Heptanoic Acids - toxicity; Histopathology; Humans; Interleukin-1alpha - metabolism; Interleukins; Kidneys; Male; Malondialdehyde; Necrosis; Occupational Medicine/Industrial Medicine; Organ Toxicity and Mechanisms; Organs; Oxidative stress; Perfluoro compounds; Perfluoroalkyl & polyfluoroalkyl substances; Perfluorooctanoic acid; Pharmacology/Toxicology; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Skin; Skin - cytology; Skin - drug effects; Skin - metabolism; Structure-Activity Relationship; Thickness; Toxicity; Toxicity Tests, Subacute - methods
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-019-02634-z

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are used in various fields but raise concerns regarding human health and environmental consequences. Among PFASs, perfluorooctanoic acid (PFOA) and short-chain perfluoroalkyl carboxylic acids (SC PFCAs) are detectable in skin-contact consumer products and have dermal absorption potential. Here, we investigated the effects of dermal exposure to PFOA and SC PFCAs using in vitro and in vivo models. Human skin equivalents were topically treated with 0.25 mM and 2.5 mM PFOA and SC PFCAs (perfluoropentanoic acid, PFPeA; perfluorohexanoic acid, PFHxA; and perfluoroheptanoic acid, PFHpA) for 6 days, and cell viability, interleukin (IL)-1α, oxidative stress markers (malondialdehyde, MDA; and 8-hydroxydeoxyguanosine, 8-OHdG), and histopathology were examined. MDA levels were significantly higher in the PFASs groups than in controls. Compared with SC PFCAs, 2.5 mM PFOA caused more IL-1α ( p