Perfluorooctanoate: Placental and lactational transport pharmacokinetics in rats.
This study was conducted to develop a quantitative understanding of the potential for gestational and lactational transfer of perfluorooctanoate (PFOA) in the rat. Time-mated female rats were dosed by oral gavage once daily at concentrations of 3, 10, or 30 mg/kg/day of the ammonium salt of PFOA (APFO) starting on gestation (G) day 4 and continuing until sacrifice. On days 10, 15, and 21G, five rats per dose level were sacrificed and blood samples were collected 2h post-dose. Embryos were collected on day 10G, amniotic fluid, placentas, and embryos/fetuses were collected on days 15 and 21G, and fetal blood samples were collected on day 21G. Five rats per dose level were allowed to deliver and nurse their litters, and on days 3, 7, 14, and 21 post-partum (PP) milk and blood samples of maternal and pup were collected 2h post-dose. All samples were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) for PFOA concentration. Concentrations of PFOA in maternal plasma and milk attained steady state during the sampling interval. The steady-state concentrations in maternal plasma were 10-15, 25-30, and 60-75 microg/mL in rats receiving 3, 10, and 30 mg/kg, respectively. Steady-state concentrations in milk were approximately 10 times less than those in maternal plasma. The concentration of PFOA in fetal plasma on day 21G was approximately half the steady-state concentration in maternal plasma. The milk concentrations appeared to be generally comparable to the concentrations in pup plasma. Pup plasma concentrations decreased from day 3PP to day 7PP, and were similar on days 7, 14, and 21PP at all dose levels. PFOA was detected in placenta (days 15 and 21G), amniotic fluid (days 15 and 21G), embryo (days 10 and 15G), and fetus (day 21G). These pharmacokinetics allow estimation of the dose to developing and nursing rat offspring following maternal exposure.
Hinderliter
Paul M
PM
DuPont Haskell Laboratory for Health and Environmental Sciences, 1090 Elkton Road, P.O. Box 50, Newark, DE 19714, USA. paul.m.hinderliter@usa.dupont.com
Mylchreest
Eve
E
Gannon
Shawn A
SA
Butenhoff
John L
JL
Kennedy
Gerald L
GL
D000818:Animals; D001711:Biotransformation; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000378:metabolism; D005466:Fluorocarbons / Q000493:pharmacokinetics*; D007774:Lactation / Q000502:physiology*; D008098:Litter Size / Q000187:drug effects; D013058:Mass Spectrometry; D008431:Maternal-Fetal Exchange; D008892:Milk / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats
D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid