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Page 2 of 15 Greene et al. J Environ Expo Assess 2024;3:12 https://dx.doi.org/10.20517/jeea.2024.09

INTRODUCTION
Per- and polyfluoroalkyl substances (PFAS) are a class of fluorinated organic compounds with numerous
past and present commercial and industrial uses. Many PFAS are of concern to public health due to their
ubiquity, persistence, solubility, and capacity to bioaccumulate in humans. These attributes pose a challenge
to the development of health-based guidance values (HBGVs) for drinking water. Following the U.S.
Environmental Protection Agency (EPA)’s 2016 issuance of lifetime Health Advisories for PFOA and
[1]
PFOS , the Minnesota Department of Health (MDH) carried out a reassessment of its own HBGVs for
these chemicals. Because PFOA and PFOS are bioaccumulative, an individual’s serum concentration can
exceed the concentration of the exposure medium, such as drinking water, and an individual’s current
serum levels are impacted by years of past exposure. Available research at the time of the reassessment
demonstrated placental transfer of PFAS from mother to infant and partitioning of PFAS into
[2-5]
[5-8]
breastmilk . These two routes of exposure suggested that infants, particularly breastfed infants, were a
potentially highly exposed subpopulation. This indicated a need for a new approach to deriving guidance
values that would incorporate both bioaccumulation and maternal transfer.

MDH addressed this need by developing a toxicokinetic (TK) model to simulate daily serum concentrations
of PFAS beginning at birth over a lifetime of daily intake and elimination of bioaccumulative PFAS . The
[9]
TK model was instrumental in the development of MDH’s 2018 HBGVs for perfluorooctanoic acid (PFOA),
perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) [10-12] . For each of these
chemicals, the model results indicated that breastfed infants had serum PFAS levels that were markedly
higher than those of formula-fed infants, as well as those of older children or adults consuming
contaminated water. The model results further indicated that it took several years for breastfed infants’
serum PFAS levels to decline to levels comparable to those of formula-fed infants. This is consistent with
empirical measurements of bioaccumulative PFAS in breastfed infants’ sera [13,14] . MDH set the HBGVs for
drinking water at levels that were protective of exclusively breastfed infants. The term “exclusively
breastfed” means that breastmilk, not formula, is the sole source of milk ; “exclusively breastfed” does not
[15]
mean breastmilk is the sole source of all nourishment.

PFAS is a very active area of scientific research; this necessitates continued attention to current research and
regular re-evaluations of HBGVs when new, impactful data become available. The HBGVs for PFOA and
PFOS were updated in 2024 [16,17] . The ensuing review process presented an opportunity and need for a
revised version of the model that would more accurately reflect the intake and elimination of PFAS as it is
currently understood. The toxicokinetic model developed in 2017 was therefore improved and updated to
reflect current scientific knowledge and understanding. These revisions included both operational changes
to the model’s calculations and chemical-specific updates reflecting new research. Here, we present the
revised and updated model and demonstrate its application to the development of a revised HBGV for
PFOA.

MATERIALS AND METHODS
Model revisions
MDH’s original TK model was developed as a Microsoft Excel spreadsheet to maximize accessibility,
[9]
transparency, and customizability . As a single-compartment model operating under first-order kinetics,
the governing equations are relatively simple. To ensure the model included the full effects of maternal
transfer, the mother was assumed to have consumed contaminated water long enough to have reached a
steady-state serum PFAS level. The infant’s serum PFAS concentration at birth was then calculated using a
placental transfer factor applied to the maternal steady-state serum concentration. On subsequent days, the
infant’s serum concentration was calculated from the previous day’s serum concentration and the current