title: Developmental toxicity of perfluorononanoic acid in mice.
abstract: Perfluorononanoic acid (PFNA) is a ubiquitous and persistent environmental contaminant. Although its levels in the environment and in humans are lower than those of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA), a steady trend of increases in the general population in recent years has drawn considerable interest and concern. Previous studies with PFOS and PFOA have indicated developmental toxicity in laboratory rodent models. The current study extends the evaluation of these adverse outcomes to PFNA in mice. PFNA was given to timed-pregnant CD-1 mice by oral gavage daily on gestational day 1-17 at 1, 3, 5 or 10mg/kg; controls received water vehicle. Dams given 10mg/kg PFNA could not carry their pregnancy successfully and effects of this dose group were not followed. Similar to PFOS and PFOA, PFNA at 5mg/kg or lower doses produced hepatomegaly in the pregnant dams, but did not affect the number of implantations, fetal viability, or fetal weight. Mouse pups were born alive and postnatal survival in the 1 and 3mg/kg PFNA groups was not different from that in controls. In contrast, although most of the pups were also born alive in the 5mg/kg PFNA group, 80% of these neonates died in the first 10 days of life. The pattern of PFNA-induced neonatal death differed somewhat from those elicited by PFOS or PFOA. A majority of the PFNA-exposed pups survived a few days longer after birth than those exposed to PFOS or PFOA, which typically died within the first 2 days of postnatal life. Surviving neonates exposed to PFNA exhibited dose-dependent delays in eye opening and onset of puberty. In addition, increased liver weight seen in PFNA-exposed offspring persisted into adulthood and was likely related to the persistence of the chemical in the tissue. Evaluation of gene expression in fetal and neonatal livers revealed robust activation of peroxisome proliferator-activated receptor-alpha (PPARα) target genes by PFNA that resembled the responses of PFOA. Our results indicate that developmental toxicity of PFNA in mice is comparable to that of PFOS and PFOA, and that these adverse effects are likely common to perfluoroalkyl acids that persist in the body.
authors.affiliation: Toxicity Assessment Division.
authors.forename: Kaberi P
authors.initials: KP
authors.lastname: Das
authors.affiliation: Toxicity Assessment Division.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Grey
authors.affiliation: Integrated Systems Toxicology Division.
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Rosen
authors.affiliation: Toxicity Assessment Division.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Wood
authors.affiliation: Toxicity Assessment Division.
authors.forename: Katoria R
authors.initials: KR
authors.lastname: Tatum-Gibbs
authors.affiliation: Research Core Unit, National Health and Environmental Effects Research Laboratory.
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Zehr
authors.affiliation: Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, United States.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Strynar
authors.affiliation: Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, United States.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lindstrom
authors.affiliation: Toxicity Assessment Division. Electronic address: lau.christopher@epa.gov.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lau
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005227:Fatty Acids; D005260:Female; D005466:Fluorocarbons / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008431:Maternal-Fetal Exchange; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced; D059467:Transcriptome
chemical_list: D005227:Fatty Acids; D005466:Fluorocarbons; D047493:PPAR alpha; C101816:perfluoro-n-nonanoic acid
keywords: CD-1 mice; Developmental toxicity; Gene expression; Perfluorononanoic acid