Evaluating the role of the dermal pathway in driving human exposure to per- and polyfluoroalkyl substances (pfas)

Ragnarsdottir, Oddny ORCID: 0000-0002-5193-6453 (2024). Evaluating the role of the dermal pathway in driving human exposure to per- and polyfluoroalkyl substances (pfas). University of Birmingham. Ph.D.

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Abstract

Per- and polyfluoroalkyl substances (PFAS) have been identified in multiple sources that come in contact with the skin, i.e., personal care products, fabrics and dust. Despite this, knowledge of dermal uptake as a source of human exposure to PFAS is lacking. The aim of this thesis was to utilize in vitro techniques to study the dermal uptake of PFAS from dust. Firstly, physiologically based extraction tests were applied to assess the dermal bioaccessibility of 17 PFAS from indoor dust to synthetic sweat sebum mixtures (SSSM). PFAS bioaccessibility in a 1:1 sweat:sebum mixture ranged from 54-92% for perfluorocarboxylic acids (PFCAs) and 61-77% for perfluorosulfonic acids (PFSAs). The presence of cosmetics significantly impacted the dermal bioaccessibility of target PFAS. Subsequently, in vitro 3D-human skin equivalent (3D-HSE) models were used to evaluate the dermal bioavailability of 17 PFAS after exposure to 500 ng/cm2 PFAS dissolved in methanol over 24-36 hours. PFPeA and PFBS displayed the highest absorbed fraction values, 58.9% and 48.7% respectively. Significant negative correlations were seen for the absorbed fraction and carbon chain length and logKOW. Steady-state flux (JSS) and permeation coefficients (Papp) were determined for target compounds with significant permeation after 36 h exposure. Combining the data produced in the bioaccessibility and bioavailability studies, the human dermal exposure from contact with dust was estimated. While dust is only one of multiple possible sources of dermal contact to PFAS, this pathway alone contributed meaningfully to the total body burden. Total PFAS exposure via dermal uptake from dust during summer ranged from 25-767 pg/kg bw/week and 91-2761 pg/kg bw/week for adults and toddlers respectively. Finally, phase I in vitro metabolism of two novel prototype PFAS in human and rat was investigated. Research on possible PFAS alternatives is urgently required as a result of proposed global restrictions and regulations on current-use PFAS. Following incubation with rat liver S9 (RL-S9) and human liver S9 (HL-S9) fractions, two and one main metabolites were detected respectively. Complete mineralization during the in vitro hepatic metabolism of these novel PFAS by HL-S9 and RL-S9 fractions was not observed.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):