Page 31 - Read Online

Page 8 of 15 Greene et al. J Environ Expo Assess 2024;3:12 https://dx.doi.org/10.20517/jeea.2024.09

initial validation used mean values of 902 days, 0.83 and 0.046 for half-life, placental transfer and breastmilk
transfer, respectively. Upper percentile values were used for breastmilk intake. As in the 2017 review of
[9]
PFOA , we compared model outputs to measured data from a cohort of exposed mothers and infants in
[6]
Germany by Fromme et al. . In this study, 37 of the 50 subjects consumed only breastmilk, 6
predominantly consumed breastmilk, 6 partially consumed breastmilk, and 1 consumed no breastmilk. The
model results and measured data from Fromme et al. were compared via a population-based approach and
an individual-based approach.

Population-based approach
Mean or 95th percentile maternal PFOA serum concentrations at delivery were entered into the
[6]
appropriate cell of the model. Modeled infant and maternal serum concentrations at 6 months of age were
then compared to their respective measured values [Table 2].

The use of mean values for all three chemical-specific parameters resulted in an underestimate of infant
serum levels. The breastmilk transfer factor has been identified as having a significant impact on predicted
infant serum levels . The available dataset for breastmilk transfer is quite limited and the timing of
[31]
collecting serum and a corresponding breastmilk sample was variable. To address the uncertainty in the
mean value, we considered alternatives to the overall mean breastmilk transfer factor of 0.046 (mean of
seven studies). One alternative was to calculate a mean value using only four of the seven studies - those in
which maternal serum and milk samples were taken within a similar timeframe. The transfer factor using
only those four studies is 0.056. The model results indicate a closer match to infant serum at 6 months, and
a less close match to maternal serum at 6 months, compared to the seven-study mean value [Table 2].

Another alternative was to calculate a 95% upper confidence limit (95UCL) on the mean of the seven
available studies. The 95UCL on the mean represents an upper limit, with 95% certainty, on the “true” mean
value. For more information, refer to the Supplementary Materials. The 95UCL on the mean was calculated
to be 0.068. For the population-based approach, infant serum concentrations calculated using this value
were a closer match to the measured data compared to the other two alternatives, while maternal serum
concentrations were slightly lower than those modeled using the seven- or four-study mean transfer factors
[Table 2].

Individual approach
Serum levels for 14 infants at 6 months of age were digitized from Fromme et al. using the online
[6]
WebPlotDigitizer tool . For each individual infant, the serum PFOA concentration at birth was entered
[32]
into the appropriate cell in the model, and the modeled infant serum concentration after 6 months of
breastfeeding was compared to the measured data. The mean of the modeled infant serum PFOA
concentrations using the three different breastmilk transfer factors (seven-study mean, four-study mean,
and 95UCL on the mean) was 65%, 75%, and 87% of the mean of the measured values, respectively.

Additional validation of the model was conducted using data from Verner et al., which provided a ratio of
infant serum PFOA level at 6 months to the mother’s serum PFOA level at delivery ; and Thomsen et al.,
[31]
who reported a maternal serum depuration rate for PFOA of 7.7% per month, or a decrease of 46.1% over
180 days . All three breastmilk transfer values yielded a ratio that was lower than the data from Verner
[33]
et al. ; the 95UCL on the mean provided the closest result (3.6 vs. 4). The 95UCL approach also yielded the
[31]
[33]
closest match to the data from Thomsen et al. (48% vs. 46.1%) [Table 3].