Repeated dose and reproductive/developmental toxicity of perfluoroundecanoic acid in rats

Abstract

-Perfluoroalkyl acids (PFAAs) are environmental contaminants that have received attention because of their possible effects on wildlife and human health. In order to obtain initial risk information on the toxicity of perfluoroundecanoic acid (PFUA), we conducted a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD test guideline 422). PFUA was administered by gavage to rats at 0 (vehicle: corn oil), 0.1, 0.3 or 1.0 mg/kg/day. At 1.0 mg/kg/day, body weight gain was inhibited in both sexes, and there was a decrease in fibrinogen in both sexes and shortening of the activated partial thromboplastin time in males. An increase in blood urea nitrogen and a decrease in total protein in both sexes and increases in alkaline phosphatase and alanine transaminase and a decrease in albumin in males were observed at 1.0 mg/kg/day. Liver weight was increased in males at 0.3 mg/kg/day and above and in females at 1.0 mg/kg/day, and this change was observed after a recovery period. In both sexes, centrilobular hypertrophy of hepatocytes was observed at 0.3 mg/kg/day and above and focal necrosis was observed at 1.0 mg/kg/day. In reproductive/developmental toxicity, body weight of pups at birth was lowered and body weight gain at 4 days after birth was inhibited at 1.0 mg/kg/day, while no dose-related changes were found in the other parameters. Based on these findings, the no observed adverse effect levels (NOAELs) for the repeated dose and reproductive/developmental toxicity were considered to be 0.1 mg/kg/day and 0.3 mg/kg/day, respectively.

Per- and polyfluorinated substances (PFASs): Environmental challenges

“…PFUnA [255] were also reported. Adult behavioral and cognitive disturbances were reported A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT 17 after exposure of rodent pups to PFAAs, usually at high doses [241][242][243].…”

Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health

“…Several experimental animal studies (n=8) reported short-term clinical effects related to PFAS exposure, with most studies showing small changes in BUN and/or creatinine concentrations across a wide range of exposure doses (42,43,45,47,48,59,79,80). However, the short-term clinical effects were variable, with some animal studies (n=3) showing no changes in BUN or creatinine at exposure doses as high as 600 mg/kg for PFOA (41,44,46), and others showing increased concentrations of both BUN and creatinine at exposure doses as low as 0.05-1.00 mg/kg for perfluoroundecanoic acid and perfluorododecanoic acid (47).…”

Tissue toxicokinetics of perfluoro compounds with single and chronic low doses in male rats

“…The reason for this extremely high accumulation of C6A is unclear: C6A does not bind with human L-FABP (Sheng et al, 2016). In general, the rate of elimination is enhanced with decreasing carbon chain length (Lau et al, 2007;Takahashi et al, 2014). However, the human serum elimination halflife of perfluoro hexane sulfonate (6-carbon PFC) is longer than that of C8S (Olsen et al, 2007).…”