Background: Perfluorinated carboxylic acids (PFCAs) are ubiquitous in human sera worldwide. Biotransformation
of the polyfluoroalkyl phosphate esters (PAPs) is a possible source of PFCA exposure,
because PAPs are used in food-contact paper packaging and have been observed in human
Objectives: We determined pharmacokinetic parameters for the PAP monoesters (monoPAPs) and PAP
diesters (diPAPs), as well as biotransformation yields to the PFCAs, using a rat model.
Methods: The animals were dosed intravenously or by oral gavage with a mixture of 4:2, 6:2,
8:2, and 10:2 monoPAP or diPAP chain lengths. Concentrations of the PAPs and PFCAs,
as well as metabolic intermediates and phase II metabolites, were monitored over time
in blood, urine, and feces.
Results: The diPAPs were bioavailable, with bioavailability decreasing as the chain length
increased from 4 to 10 perfluorinated carbons. The monoPAPs were not absorbed from
the gut; however, we found evidence to suggest phosphate-ester cleavage within the
gut contents. We observed biotransformation to the PFCAs for both monoPAP and diPAP
Conclusions: Using experimentally derived biotransformation yields, perfluorooctanoic acid (PFOA)
sera concentrations were predicted from the biotransformation of 8:2 diPAP at concentrations
observed in human serum. Because of the long human serum half-life of PFOA, biotransformation
of diPAP even with low-level exposure could over time result in significant exposure
to PFOA. Although humans are exposed directly to PFCAs in food and dust, the pharmacokinetic
parameters determined here suggest that PAP exposure should be considered a significant
indirect source of human PFCA contamination.