Gestational and lactational exposure to potassium perfluorooctanesulfonate (K+PFOS) in rats: developmental neurotoxicity.
Perfluorooctanesulfonate (PFOS), a persistent and bioaccumulative compound, is widely distributed in humans and wildlife. Exposure of the human fetus and neonate to PFOS can occur in utero and via the mother's milk, respectively. Developmental studies have been conducted with PFOS in the past, including some developmental neurotoxicity endpoints. The objective of this study was to evaluate the functional and morphological changes to the nervous system in rats having gestational and lactational exposures to PFOS per current test guidelines (EPA OPPTS 870.6300 and OECD 426). Female SD rats (25/dosage group) were given daily oral doses of either 0.0, 0.1, 0.3, or 1.0mg/kg-d potassium PFOS (K(+)PFOS) from gestation day (GD) 0 through postnatal day (PND) 20. Offspring were observed through PND 72 for growth, maturation, motor activity, learning and memory, acoustic startle reflex, various behavioral manifestations, and brain weight. Specimens were taken from dams, fetuses, and pups for serum and tissue PFOS concentration, thyroid status endpoints, and liver mRNA transcript analysis, and those results are reported in a companion article. No significant effect was noted on maternal health or reproductive outcomes from dosing of maternal rats with K(+)PFOS throughout gestation. Maternal body weights were statistically significantly lower in the 1.0mg/kg-d dosage group from PND 4 through the end of lactation. Offspring from K(+)PFOS-treated maternal groups did not differ significantly from controls with respect to birth weight, growth, age and weight at attainment of sexual maturation, learning and memory, acoustic startle, various behavioral endpoints, and brain weight. Male offspring from the 1.0mg/kg-d maternal treatment group displayed increased motor activity and reduced habituation on PND 17 but not on PND 13, 21, and 61. The maternal no-observed-adverse-effect-level (NOAEL) was 0.3mg/kg-d based on decreased body weights observed in lactation. The maternal dose associated with the NOAEL for male offspring was 0.3mg/kg-d based on increased motor activity and reduced habituation in the 1.0mg/kg-d maternal dose-group male offspring on PND 17. The maternal dose associated with the NOAEL for female offspring was >1.0mg/kg-d. Mean serum concentrations of PFOS reported in a companion article for the 0.3mg/kg-d group maternal rats are several hundred times higher than those reported for females in the United States general population.
Butenhoff
John L
JL
Medical Department, 3M Company, 3M Center 220-6W-08, Saint Paul, MN 55144, United States. Electronic address: jlbutenhoff@mmm.com.
Ehresman
David J
DJ
Medical Department, 3M Company, 3M Center 220-6W-08, Saint Paul, MN 55144, United States.
Chang
Shu-Ching
SC
Medical Department, 3M Company, 3M Center 220-6W-08, Saint Paul, MN 55144, United States.
Parker
George A
GA
Biotechnics, LLC, Hillsborough, NC 27278, United States.
Stump
Donald G
DG
WIL Research Laboratories, Ashland, OH 44805, United States.
D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D005865:Gestational Age; D017408:Guidelines as Topic; D007774:Lactation / Q000187:drug effects*; D018811:Maternal Exposure; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects
D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; C076994:perfluorooctane sulfonic acid