title: Prenatal perfluorooctanoic acid exposure in CD-1 mice: low-dose developmental effects and internal dosimetry.
abstract: Perfluorooctanoic acid (PFOA) is an environmental contaminant that causes adverse developmental effects in laboratory animals. To investigate the low-dose effects of PFOA on offspring, timed-pregnant CD-1 mice were gavage dosed with PFOA for all or half of gestation. In the full-gestation study, mice were administered 0, 0.3, 1.0, and 3.0 mg PFOA/kg body weight (BW)/day from gestation days (GD) 1-17. In the late-gestation study, mice were administered 0, 0.01, 0.1, and 1.0 mg PFOA/kg BW/day from GD 10-17. Exposure to PFOA significantly (p < 0.05) increased offspring relative liver weights in all treatment groups in the full-gestation study and in the 1.0 mg PFOA/kg group in the late-gestation study. In both studies, the offspring of all PFOA-treated dams exhibited significantly stunted mammary epithelial growth as assessed by developmental scoring. At postnatal day 21, mammary glands from the 1.0 mg/kg GD 10-17 group had significantly less longitudinal epithelial growth and fewer terminal end buds compared with controls (p < 0.05). Evaluation of internal dosimetry in offspring revealed that PFOA concentrations remained elevated in liver and serum for up to 6 weeks and that brain concentrations were low and undetectable after 4 weeks. These data indicate that PFOA-induced effects on mammary tissue (1) occur at lower doses than effects on liver weight in CD-1 mice, an observation that may be strain specific, and (2) persist until 12 weeks of age following full-gestational exposure. Due to the low-dose sensitivity of mammary glands to PFOA in CD-1 mice, a no observable adverse effect level for mammary developmental delays was not identified in these studies.
authors.affiliation: Curriculum in Toxicology, University of North Carolina, School of Medicine, Chapel Hill, North Carolina 25799, USA.
authors.forename: Madisa B
authors.initials: MB
authors.lastname: Macon
authors.forename: LaTonya R
authors.initials: LR
authors.lastname: Villanueva
authors.forename: Katoria
authors.initials: K
authors.lastname: Tatum-Gibbs
authors.forename: Robert D
authors.initials: RD
authors.lastname: Zehr
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Strynar
authors.forename: Jason P
authors.initials: JP
authors.lastname: Stanko
authors.forename: Sally S
authors.initials: SS
authors.lastname: White
authors.forename: Laurence
authors.initials: L
authors.lastname: Helfant
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Fenton
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000097:blood / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005466:Fluorocarbons / Q000097:blood / Q000633:toxicity*; D005865:Gestational Age; D008099:Liver / Q000187:drug effects; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008815:Mice, Inbred Strains; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D012680:Sensitivity and Specificity
chemical_list: D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid