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Analysis of PFOA in Dosed CD1 Mice Part 1: Methods Development for the Analysis of Tissues and Fluids from Pregnant and Lactating Mice and Their Pups
Citation:
Reiner, J. L., S. F. Nakayama, A. DELINSKY, J. STANKO, S. E. FENTON, A. B. LINDSTROM, AND M. J. STRYNAR. Analysis of PFOA in Dosed CD1 Mice Part 1: Methods Development for the Analysis of Tissues and Fluids from Pregnant and Lactating Mice and Their Pups. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 27(3-4):365-372, (2009).
Impact/Purpose:
The National Exposure Research Laboratory′s (NERL) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA′s mission to protect human health and the environment. HEASD′s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA′s strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
Description:
The number of studies involving the analysis of perfluorooctanoic acid (PFOA) has 33 increased recently because PFOA is routinely detected in human blood samples from around the world. Recent studies with mice have shown that dosing pregnant dams with PFOA during gestation gives rise to a dose-dependent mortality in the litters, a reduction in neonatal body weight for the surviving pups, and subsequent deficits in mammary gland development when compared to control animals. The actual body burdens of PFOA in dams and pups associated with these endpoints have not been determined, in part due to a lack of robust analytical methods for these matrices. The goal of the current study was to develop reliable methods with acceptable performance characteristics for the analysis of PFOA in several matrices relevant to pregnant mouse studies. Dam and pup serum, amniotic fluid, urine, milk, mammary tissue, and whole mouse pups were isolated for method development and analysis. The resulting method provided excellent accuracy (92.1%-111%) and reproducibility (relative standard deviation 4.3%-21%) making them very useful for future studies. These methods were then applied to dosed animal fluids and tissues in order to conduct a thorough evaluation of the pharmacokinetics in utero. Resulting tissue specific measurements of PFOA in serum, amniotic fluid, urine, milk, mammary tissue, and whole pup homogenate will be used to more completely describe the dose-response relationships for the most sensitive health outcomes and inform pharmacokinetic models that are being developed and evaluated.
