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Toxicological evaluation of ammonium perfluorobutyrate in rats: Twenty-eight-day and ninety-day oral gavage studies
Butenhoff, J., S. Chang, G. A. Parker, C. LAU, F. M. van Otterdijk, J. A. Bjork, D. J. Ehresman, K. Das, P. H. Leider, AND K. Wallace. Toxicological evaluation of ammonium perfluorobutyrate in rats: Twenty-eight-day and ninety-day oral gavage studies. REPRODUCTIVE TOXICOLOGY. Elsevier Science Ltd, New York, NY, 33(4):513-530, (2012).
Sequential 28-day and 90-day oral toxicity studies were performed in male and female rats with ammonium perfluorobutyrate (NH4+PFBA) at doses up to 150 and 30 mg/kg/d, respectively. Ammonium perfluorooctanoate was used as a comparator at a dose of 30 mg/kg/d in the 28-d study. Female rats were unaffected by NH4+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 PPARa and CAR as well as the thyroid receptor, and decreased expression of CyplAl (Ah receptor-regulated). No observable adverse effect levels (NOAELs) were 6 and >150 mg/kg/d for male and female rats in the 28-day study and 6 and >30 mg/kg/d in the 90-dat study, respectively.
Perfluorobutyrate, a chemical manufactured by 3M in the past, has been detected in the surface water and drinking water wells at locations near the manufacturing plant and disposal sites in Minnesota. This discovery has drawn considerable interests from the Minnesota Department of Health (MDH) as well as concerns from the local residents. A major concern stems from the previous findings with perfluorooctanoic acid (PFOA), a chemical related to PFBA, where developmental and systemic toxicities in the laboratory animal models have been noted. This paper is the last of a series of three papers arisen from collaborative studies between investigators at 3M, University of Minnesota and EPA, describing the adverse effects of PFBA in rats, mice and humans, and focuses on adult rats after 28-days or 90-days of chemical treatment. PFBA was found to increase liver weight (similar to other perfluorinated chemicals), enhance hepatic gene expression of xenosensor nuclear receptors PPARa and CAR, reduce serum cholesterol and reduced serum thyroxine levels. These changes were seen preferentially in the male rats, and returned to control levels upon recovery from chemical exposure. These findings will be instrumental to the risk assessment report being drafted by the MDH, under the mandate of the state legislature, and provide a valuable database for EPA program offices for risk assessment of the entire class of perfluorinated chemicals in the near future.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
TOXICOLOGY ASSESSMENT DIVISION
DEVELOPMENTAL TOXICOLOGY BRANCH