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.
The number of studies involving the analysis of perfluorooctanoic acid (PFOA) has 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.
Reiner
Jessica L
JL
Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Nakayama
Shoji F
SF
Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Delinsky
Amy D
AD
Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Stanko
Jason P
JP
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Fenton
Suzanne E
SE
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Lindstrom
Andrew B
AB
Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Strynar
Mark J
MJ
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: strynar.mark@epa.gov.
D000653:Amniotic Fluid / Q000737:chemistry; D000818:Animals; D000831:Animals, Newborn; D001774:Blood Chemical Analysis / Q000379:methods; D001822:Body Burden; D002210:Caprylates / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D007774:Lactation; D018811:Maternal Exposure; D051379:Mice; D008815:Mice, Inbred Strains; D008892:Milk / Q000737:chemistry; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000652:urine; D013997:Time Factors; D014018:Tissue Distribution; D016482:Urinalysis
D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; C023036:perfluorooctanoic acid