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Page 10 of 15 Greene et al. J Environ Expo Assess 2024;3:12 https://dx.doi.org/10.20517/jeea.2024.09

serum concentration. Infants and young children were not included in the CDC National Report, but the
available data on placental transfer indicate that newborn infants would have PFOA body burdens similar to
those of their mothers following months of breastfeeding. Studies of exclusively breastfed infants [6,13] found
serum PFOA levels approximately 3-fold higher than their mothers. The available data therefore suggest
that an RSC value equal to the floor value of 20% is appropriate for all life stages.

The revised model was used to determine a noncancer HBGV for PFOA using a maximum allowable serum
concentration of 0.19 ng/mL, i.e., the reference serum concentration multiplied by the RSC (0.93 ng/mL ×
[9]
0.2). As was done in MDH’s 2017 review , the model was applied to two scenarios: (1) an infant consuming
formula prepared with contaminated water, and consuming contaminated water for a lifetime; and (2) an
infant breastfed for 12 months, followed by a lifetime of consuming contaminated water. Both of these
model applications were RME scenarios using a mixture of central tendency and upper percentile model
parameters. Under scenario 1, a drinking water concentration of 1 ng/L (0.001 µg/L) maintained a serum
PFOA concentration below the target level of 0.19 ng/mL throughout the simulated lifetime [Figure 1].
Under scenario 2, a drinking water concentration of 0.24 ng/L (0.00024 µg/L), approximately four times
lower than scenario 1, was required to maintain a serum PFOA concentration below 0.19 ng/mL throughout
the simulated lifetime [Figure 2]. Thus, the noncancer HBGV for PFOA was set at 0.24 ng/L to ensure
adequate protection of the most highly exposed population, breastfed infants.

For both model scenarios, the combined effect of model updates and chemical-specific parameter updates
resulted in lower modeled serum PFOA concentrations compared to the 2017 model results using the same
drinking water concentration (dashed blue lines in Figures 1 and 2). However, the significantly lower
epidemiologic-based reference serum concentration of 0.93 ng/mL (compared to the laboratory animal-
based value of 130 ng/mL used in 2017) was the major factor in lowering the noncancer HBGV from 35 to
0.24 ng/L.

[37]
MDH also develops separate HBGVs based on cancer risk when relevant data are available . In addition to
the noncancer guidance value, MDH also developed a cancer HBGV of 0.0079 ng/L for PFOA . The TK
[16]
model was not used to derive the cancer HBGV, which is based on an incremental lifetime cancer risk level
of 1 in 100,000.

Impact of model revisions
The 57% reduction in modeled peak serum concentrations between the 2017 and 2024 model runs is the net
effect of all model improvements and parameter updates [Tables 4 and 5]. The relative impacts of these
changes were compared by running the RME breastfed infant scenario using the original and revised
models with an identical set of chemical parameters and a drinking water concentration set to the
noncancer HBGV of 0.24 ng/L. The non-chemical-specific model improvements [mass balance (including
maternal loss to the infant on Day 1), body weight updates, milk intakes, and water intakes] were then
added individually to the model [Table 4]. The improvements in the conservation of mass were by far the
most influential changes, with the other non-chemical-specific changes having a negligible effect on the
peak serum concentration.

The relative effects of the chemical-specific model parameters in the revised model were compared by
implementing the PFOA parameter changes individually, using the set of 2017 parameters for PFOA as a
baseline [Table 5]. Changes to the V parameter had the largest effect on the peak serum concentration,
d
followed by the milk:maternal serum ratio and the t .
½