title: Toxicological evaluation of ammonium perfluorobutyrate in rats: twenty-eight-day and ninety-day oral gavage studies.
abstract: Sequential 28-day and 90-day oral toxicity studies were performed in male and female rats with ammonium perfluorobutyrate (NH(4)(+)PFBA) at doses up to 150 and 30mg/kg-d, respectively. Ammonium perfluorooctanoate was used as a comparator at a dose of 30mg/kg-d in the 28-day study. Female rats were unaffected by NH(4)(+)PFBA. Effects in males included: increased liver weight, slight to minimal hepatocellular hypertrophy; decreased serum total cholesterol; and reduced serum thyroxin with no change in serum thyrotropin. During recovery, liver weight, histological, and cholesterol effects were resolved. Results of RT-qPCR were consistent with increased transcriptional expression of the xenosensor nuclear receptors PPARα and CAR as well as the thyroid receptor, and decreased expression of Cyp1A1 (Ah receptor-regulated). No observable adverse effect levels (NOAELs) were 6 and >150mg/kg-d for male and female rats in the 28-day study and 6 and >30mg/kg-d in the 90-dat study, respectively.
authors: Medical Department, 3M Company, 3M Center 220-06-W-08, St. Paul, MN, USA. Electronic address: jlbutenhoff@mmm.com.
authors: John L
authors: JL
authors: Butenhoff
authors: Department of Biochemistry and Molecular Biology, School of Medicine, University of Minnesota, Duluth, MN, USA. Electronic address: jbjork1@d.umn.edu.
authors: James A
authors: JA
authors: Bjork
authors: Medical Department, 3M Company, 3M Center 220-06-W-08, St. Paul, MN, USA. Electronic address: s.chang@mmm.com.
authors: Shu-Ching
authors: SC
authors: Chang
authors: Medical Department, 3M Company, 3M Center 220-06-W-08, St. Paul, MN, USA. Electronic address: djehresman@mmm.com.
authors: David J
authors: DJ
authors: Ehresman
authors: Biotechnics, Inc., Hillsborough, NC, USA. Electronic address: gparker@biotechnics-inc.com.
authors: George A
authors: GA
authors: Parker
authors: United States Environmental Protection Agency, National Health and Environmental Effects Laboratory, Research Triangle Park, NC, USA. Electronic address: das.kaberi@epa.gov.
authors: Kaberi
authors: K
authors: Das
authors: United States Environmental Protection Agency, National Health and Environmental Effects Laboratory, Research Triangle Park, NC, USA. Electronic address: lau.christopher@epa.gov.
authors: Christopher
authors: C
authors: Lau
authors: Medical Department, 3M Company, 3M Center 220-06-W-08, St. Paul, MN, USA. Electronic address: phlieder1@mmm.com.
authors: Paul H
authors: PH
authors: Lieder
authors: NOTOX B. V., 5231 DD 's-Hertogenbosch, The Netherlands. Electronic address: francois.van.otterdijk@notox.nl.
authors: François M
authors: FM
authors: van Otterdijk
authors: Department of Biochemistry and Molecular Biology, School of Medicine, University of Minnesota, Duluth, MN, USA. Electronic address: kwallace@d.umn.edu.
authors: Kendall B
authors: KB
authors: Wallace
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005466:Fluorocarbons / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D059550:Toxicity Tests, Subchronic / Q000379:methods*; D014874:Water Pollutants, Chemical / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D005466:Fluorocarbons; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014874:Water Pollutants, Chemical; C033094:perfluorobutyric acid; D002784:Cholesterol