Table 7

PFBA (ammonium salt)

CAS No. not given

28.9% solution in distilled water.

Butenhoff et al. (2012a)

Sprague-Dawley rats

Male and female

10/sex/dose.

Recovery group:

Male and female

10/sex/dose.

0, 6, 30 or 150 (actual dose 0, 5.3, 25.4 or 130.2).

Milli-Q or Milli-U water

Gavage,

28 days,

Non-GL study,

GLP not stated.

Recovery group:

0, 6, 30 or 150 (actual dose 0, 5.3, 25.4 or 130.2)

3 weeks.

Treatment:

Males (mean ± SD):

At 6 mg/kg bw/day

Serum: 24.65 ± 17.63

Liver: 7.49 ± 4.46.

At 30 mg/kg bw/day

Serum: 38.40 ± 23.15

Liver: 14.72 ± 8.15.

Females:

At 150 mg/lg bw/day:

10.30 ± 4.50.

Recovery:

Males:

At 150 mg/kg bw/day:

Serum: 1.07 ± 0.27

Liver: 0.33±0.10.

Females:

NR.

Males (mean ± SD):

↑ absolute liver weight (g): 8.08 ± 0.73 vs 10.26 ± 1.43,

↑ ALP (IU): 234 ± 51 vs 320 ± 67.

↓ cholesterol (mmol/L): 1.37 ± 0.27 vs 1.09 ± 0.20.

↑ mRNA of Acox, Ugt 1A1 and CYP4A1 in liver (data only reported in figures).

↓ mRNA for Cyp1A1, Ugt 1A6 and Ugt 2A in liver (data only reported in figures).

Females:

No adverse effects reported (NOAEL is highest dose tested).

Recovery:

Males (mean ± SD):

↑ TP (g/L): 64.5 ± 1.7 vs 67.3 ± 1.9.

Absolute liver weight comparable to controls (g): 9.53 ± 1.42 vs 9.15 ± 0.50.

Cholesterol comparable to controls (mmol/L): 1.57 ± 0.34 vs 1.70 ± 0.28.

Females:

No adverse effects reported (NOAEL is highest dose tested).

Males:

6 / 30.

Female:

150 / NA.

Recovery:

Males:

30 / 150*.

Females:

150 / NA*.

Male rats appeared more sensitive than female rats in both the 28-day and 90-day studies. The observed reduced sensitivity of females likely is a result, in part, of the greater elimination rate of PFBA in female rats as compared to males.

Liver hypertrophy was observed in the absence of either clinical or microscopic evidence of liver injury and was fully reversible on cessation of treatment.

The lowering of serum total cholesterol observed in 28-day study at 30 and 150 mg/kg-d likely resulted, at least in part, from events tied to activation of PPAR based on the observation of increased transcription levels of Acox and Cyp4a1 at these dose levels.

K1

This was a comparative study investigating oral toxicity of PFBA and PFOA.

Body weight was not affected at the LOAEL in males or females.

Liver weight and cholesterol in male rats returned to control values after 3 weeks recovery.

Hepatocellular hypertrophy was only seen at the highest dose.

Study was funded by the U.S. Environmental Protection Agency. Authors are affiliated to 3M Company.

PFBA (ammonium salt)

CAS No. not given

28.9% solution in distilled water.

Butenhoff et al. (2012a)

Sprague-Dawley rats

Male and female

10/sex/dose.

Recovery group:

Male and female

7/sex/dose.

0, 1.2, 6 or 30

(actual dose 0, 1.4, 6.9 or 32.4).

Milli-Q or Milli-U water.

Gavage,

90 days,

Non-GL study,

GLP not stated.

Recovery group:

0 and 30 (actual doses, 0 and 32.4),

3 weeks.

At 6 mg/kg bw/day in males after treatment (mean ± SD):

Serum: 13.63 ± 9.12

Liver: 3.07 ± 2.03.

At 30 mg/kg bw/day in males after treatment Serum: 52.22 ± 24.89

Liver: 16.09 ± 9.06.

At 30 mg/kg bw/day in females after treatment Serum:  5.15 ± 3.29

Liver: 0.91 ± 0.55.

At 0 mg/kg bw/day in males after recovery Serum:  <0.01

Liver: <0.05.

At 30 mg/kg bw/day in males after recovery Serum:  <0.01

Liver: <0.05.

Males (mean ± SD):

↑ absolute liver weight (g): 10.92 ± 1.17 vs 13.41 ± 2.01.

↑ ALP (IU): 146 ± 38 vs 193 ± 55.

↓ TP (g/L): 71.4 ± 3.0 vs.67.8 ± 3.0.

↓ bilirubin (µmol/L): 2.8 ± 0.

3 vs 2.2 ± 0.3.

↑ hepatocellular hypertrophy (0 vs 9; 5 minimum and 4 slight).

↑ mRNA of Acox, UGT1A1, CYP4A1, malic enzyme and Por (data only reported in figures).

↓ mRNA for Cyp1A1 in liver (data only reported in figures).

Females:

↓ bilirubin (µmol/L): 3.8 ± 0.6 vs 3.1 ± 0.5.

Recovery:

Males (mean ± SD):

Absolute liver weight comparable to controls (g): 10.67 ± 0.74 vs 11.13 ± 1.79

TP comparable to controls – data not shown.

Bilirubin comparable to controls – data not shown

Hepatocellular hypertrophy comparable to controls (0 vs 0).

Females:

Bilirubin: comparable to controls – data not shown.

Males:

6 / 30.

Female:

30 / NA.

Recovery:

Males:

30 / NA*.

Females:

150 / NA*.

Male rats appeared more sensitive than female rats in both the 28-day and 90-day studies. The observed reduced sensitivity of females likely is a result, in part, of the greater elimination rate of PFBA in female rats as compared to males.

Liver hypertrophy was observed in the absence of either clinical or microscopic evidence of liver injury and was fully reversible on cessation of treatment.

K1

This was a comparative study investigating oral toxicity of PFBA and PFOA.

NOAEL in males is based on increased liver weight that is likely to be adaptive, in the absence of clinical or pathological symptoms.

3 animals in the recovery group were used for ocular parameters hence only 7 animals were used for other parameters.

Study was funded by the U.S. Environmental Protection Agency. Authors are affiliated to 3M Company.

PFBA

CAS No. not given

Purity not given.

Foreman et al. (2009)

SV/129 mice (WT, PPAR-α null and humanised. PPAR-α)

Male, 

10/dose.

0, 35, 175 or 350,

Water,

Gavage,

28 days,

Non-GL study,

GLP not stated.

Data only reported in figures.

WT (mean ± SEM)

↑ relative liver weight (Data only reported in figures).

↑ Hepatocyte hypertrophy (total): 0 vs 10.

↑ ALT (U/L): 5.29 ± 3.38.

↑ hepatic replicative DNA. synthesis: 1.8 ± 0.6 vs 19.1 ± 11.7.

↑ mRNA of Cyp4A10 (Data only reported in figures).

↑ mRNA of ACO (Data only reported in figures).

Recovery not assessed.

Males:

NA / 35*

Administration of PFBA caused a PPAR-α–dependent increase in average liver weight and hepatocyte hypertrophy because these changes were found in wild-type mice but not in similarly treated PPAR-α null mice. The relative increase in liver weight and hepatocyte hypertrophy was also observed in humanized PPAR-α mice.

K2

This study investigated if PPAR-α modulates the hepatic response to PFBA exposure and if there is a species difference in PPAR-α activities so used WT, PPAR-α null and humanised PPAR-α mice

Only wild-type data presented in this report.

Only male animals were used.

Study was funded by 3M.