Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: maternal and prenatal evaluations.
The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.
Thibodeaux
Julie R
JR
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Hanson
Roger G
RG
Rogers
John M
JM
Grey
Brian E
BE
Barbee
Brenda D
BD
Richards
Judy H
JH
Butenhoff
John L
JL
Stevenson
Lisa A
LA
Lau
Christopher
C
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D017738:Alkanesulfonic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D005466:Fluorocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D018811:Maternal Exposure; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D013723:Teratogens / Q000493:pharmacokinetics / Q000633:toxicity*; D013974:Thyroxine / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; D013723:Teratogens; D014280:Triglycerides; D014284:Triiodothyronine; C076994:perfluorooctane sulfonic acid; D013974:Thyroxine