Reliability of Toxicokinetic Modelling for PFAS Exposure Assessment in Contaminated Water in Northern Italy

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Aug 21

PMID 39166031

Authors

L Vaccari

A Ranzi

C Canova

G Ghermandi

S Giannini

G Pitter

F Russo

J Stefanelli

S Teggi

A Vantini

M Z Jeddi

T Fletcher

A Colacci

Affiliations

Soon will be listed here.

Abstract

Introduction: Long-term contamination of tap water and groundwater by perfluoroalkyl and polyfluoroalkyl substances (PFASs) has been documented in the Veneto region of northern Italy. This study aimed to assess the exposure of individuals residing in the contaminated area and to test several toxicokinetic (TK) models of varying complexities to identify an efficient method for predicting perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) concentrations in human serum using observed data.The ultimate goal is to provide public health officials with guidance on selecting the appropriate TK model for specific contexts, a reliable and rapid tool to support human bio-monitoring (HBM) studies.

Methods: Two simpler empirical TK models and a more complex multi-compartment physiologically based toxicokinetic (PBTK) model were compared with individual and aggregate data from an HBM study. In addition, the PBPK model was modified by adjusting input parameters and introducing new terms into the equations within the original model code. These modifications aimed to optimize the results compared to the original model, with some versions incorporating adjustments to account for the influence of menstruation in women. All models were evaluated to understand their strengths and weaknesses, providing guidance on the appropriate model to use according to specific scenarios.

Results: The results obtained from the tested models were quite similar, with significant improvements observed only in the modified models. Simpler models also provided satisfactory results in scenarios involving low PFOS serum concentrations and recent exposure cessation. In many cases, predictions demonstrated high accuracy, particularly at the aggregate level and for women.

Conclusions: These findings suggest that environmental protection agencies and health authorities may benefit from employing the tested models at the aggregate level as an initial step in HBM studies, rather than conducting more invasive and expensive screening campaigns.

References

Frisbee S, Brooks Jr A, Maher A, Flensborg P, Arnold S, Fletcher T . The C8 health project: design, methods, and participants. Environ Health Perspect. 2010; 117(12):1873-82. PMC: 2799461. DOI: 10.1289/ehp.0800379. View

Loccisano A, Longnecker M, Campbell Jr J, Andersen M, Clewell 3rd H . Development of PBPK models for PFOA and PFOS for human pregnancy and lactation life stages. J Toxicol Environ Health A. 2012; 76(1):25-57. PMC: 3502013. DOI: 10.1080/15287394.2012.722523. View

Thompson J, Lorber M, Toms L, Kato K, Calafat A, Mueller J . Use of simple pharmacokinetic modeling to characterize exposure of Australians to perfluorooctanoic acid and perfluorooctane sulfonic acid. Environ Int. 2010; 36(4):390-397. DOI: 10.1016/j.envint.2010.02.008. View

Wong F, MacLeod M, Mueller J, Cousins I . Enhanced elimination of perfluorooctane sulfonic acid by menstruating women: evidence from population-based pharmacokinetic modeling. Environ Sci Technol. 2014; 48(15):8807-14. DOI: 10.1021/es500796y. View

Shin H, Vieira V, Ryan P, Detwiler R, Sanders B, Steenland K . Environmental fate and transport modeling for perfluorooctanoic acid emitted from the Washington Works Facility in West Virginia. Environ Sci Technol. 2011; 45(4):1435-42. DOI: 10.1021/es102769t. View

Verner M, Longnecker M . Comment on "enhanced elimination of perfluorooctanesulfonic Acid by menstruating women: evidence from population-based pharmacokinetic modeling". Environ Sci Technol. 2015; 49(9):5836-7. DOI: 10.1021/acs.est.5b00187. View

Ehresman D, Froehlich J, Olsen G, Chang S, Butenhoff J . Comparison of human whole blood, plasma, and serum matrices for the determination of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other fluorochemicals. Environ Res. 2006; 103(2):176-84. DOI: 10.1016/j.envres.2006.06.008. View

Vaccari M, Serra S, Ranzi A, Aldrovandi F, Maffei G, Mascolo M . In vitro evaluation of the carcinogenic potential of perfluorinated chemicals. ALTEX. 2024; 41(3):439-456. DOI: 10.14573/altex.2310281. View

Hoffman K, Webster T, Bartell S, Weisskopf M, Fletcher T, Vieira V . Private drinking water wells as a source of exposure to perfluorooctanoic acid (PFOA) in communities surrounding a fluoropolymer production facility. Environ Health Perspect. 2010; 119(1):92-7. PMC: 3018506. DOI: 10.1289/ehp.1002503. View

10.

Andersen M, Clewell 3rd H, Tan Y, Butenhoff J, Olsen G . Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in monkeys--probing the determinants of long plasma half-lives. Toxicology. 2006; 227(1-2):156-64. DOI: 10.1016/j.tox.2006.08.004. View

11.

Hundley S, Sarrif A, Kennedy G . Absorption, distribution, and excretion of ammonium perfluorooctanoate (APFO) after oral administration to various species. Drug Chem Toxicol. 2006; 29(2):137-45. DOI: 10.1080/01480540600561361. View

12.

Ingelido A, Marra V, Abballe A, Valentini S, Iacovella N, Barbieri P . Perfluorooctanesulfonate and perfluorooctanoic acid exposures of the Italian general population. Chemosphere. 2010; 80(10):1125-30. DOI: 10.1016/j.chemosphere.2010.06.025. View

13.

Xu Y, Fletcher T, Pineda D, Lindh C, Nilsson C, Glynn A . Serum Half-Lives for Short- and Long-Chain Perfluoroalkyl Acids after Ceasing Exposure from Drinking Water Contaminated by Firefighting Foam. Environ Health Perspect. 2020; 128(7):77004. PMC: 7351026. DOI: 10.1289/EHP6785. View

14.

Johanson G, Gyllenhammar I, Ekstrand C, Pyko A, Xu Y, Li Y . Quantitative relationships of perfluoroalkyl acids in drinking water associated with serum concentrations above background in adults living near contamination hotspots in Sweden. Environ Res. 2022; 219:115024. DOI: 10.1016/j.envres.2022.115024. View

15.

Harada K, Inoue K, Morikawa A, Yoshinaga T, Saito N, Koizumi A . Renal clearance of perfluorooctane sulfonate and perfluorooctanoate in humans and their species-specific excretion. Environ Res. 2005; 99(2):253-61. DOI: 10.1016/j.envres.2004.12.003. View

16.

Loccisano A, Campbell Jr J, Andersen M, Clewell 3rd H . Evaluation and prediction of pharmacokinetics of PFOA and PFOS in the monkey and human using a PBPK model. Regul Toxicol Pharmacol. 2010; 59(1):157-75. DOI: 10.1016/j.yrtph.2010.12.004. View

17.

Barry V, Winquist A, Steenland K . Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect. 2013; 121(11-12):1313-8. PMC: 3855514. DOI: 10.1289/ehp.1306615. View

18.

Knutsen H, Alexander J, Barregard L, Bignami M, Bruschweiler B, Ceccatelli S . Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food. EFSA J. 2020; 16(12):e05194. PMC: 7009575. DOI: 10.2903/j.efsa.2018.5194. View

19.

Steenland K, Jin C, MacNeil J, Lally C, Ducatman A, Vieira V . Predictors of PFOA levels in a community surrounding a chemical plant. Environ Health Perspect. 2009; 117(7):1083-8. PMC: 2717134. DOI: 10.1289/ehp.0800294. View

20.

Fabrega F, Nadal M, Schuhmacher M, Domingo J, Kumar V . Influence of the uncertainty in the validation of PBPK models: A case-study for PFOS and PFOA. Regul Toxicol Pharmacol. 2016; 77:230-9. DOI: 10.1016/j.yrtph.2016.03.009. View