Table 3

PFOA

CAS No. not given

96%.

Cheng and Klaassen (2008)

C57BL/6, mice

Male

5/dose.

0 or 40

Propylene glycol:water

i.p.

Single dose

Non-GL study

GLP not stated.

NR

Males:

↑ mRNA of cyp2B10,

3A11 and 4A14 in liver (data only reported in figures).

↑ protein levels of cyp2B and 4A in liver (data only reported in figures).

Recovery not assessed.

Males:

NA / 40*

PFOA increased the expression of Cyp2B10 and 4A14 in mouse liver.

K2

This study investigated if expression of cytochrome P450 is altered by PFOA and PFDA and the regulatory mechanisms involved.

i.p. route of exposure was used.

Only male animals were used.

Study was funded by National Institutes of Health grants.

PFOA (ammonium salt)

CAS No. not given

97%.

Das et al. (2017)

SV129 mice (wild type and PPAR-α null)

Male

4/dose.

0 or 10 m/kg bw/day.

Deionized water,

Gavage,

7 days,

Non-GL study,

GLP not stated.

NR

Males:

↑ absolute and relative liver weight (data only reported in figures).

↑ lipid and TGs (data only reported in figures).

Changes in mRNA related to transport, fatty acid, TG and cholesterol synthesis and omega oxidation.

Recovery not assessed.

Males:

NA / 10

PFOA caused extensive micro and macro-vesicular steatosis in hepatocytes and that the steatosis was associated with increases in the accumulation of TG in the liver.

K2

The study investigated whether structurally-diverse PFAS increased liver TG levels and caused steatosis and investigated mechanisms involved.

Only 4 male animals were used.

Study was funded by US Environmental Protection Agency.

PFOA (ammonium salt)

CAS No. not given

98%.

Elcombe et al. (2010)

SD (CD) rats Male  30/dose.

0 or 300 ppm in diet equivalent to 27**.

Powdered RMI feed,

Diet,

1 day,

Non-GL study,

GLP not stated.

NR

Males (mean ± SD):

↑ hepatic cell proliferation (%): 0.22 ± 0.14 vs 0.74 ± 0.55,

↓ liver DNA concentration (mg DNA/g liver): 2.20 ± 0.26 vs 1.92 ± 0.11,

↑ AST (U/L): 177.70 ± 33.27 vs 132.57 ± 36.79.

↑ protein expression of CYP2B1/2, CYP3A1 and CYPA1: data only provided in figures.

↓ periportal hepatocellular glycogen: grade 1.

Males: 

NA / 27*

The objective of the work was to characterize PFOA-induced hepatomegaly in male rats, particularly with respect to the potential role of PPAR-α -mediated cell proliferation and possible decreased apoptosis.

Clinical chemistry findings were consistent with those associated with PPAR activation, notably decreased serum total cholesterol and triglycerides.

APFO did not increase activities of either ALT or AST, consistent with a lack of histologically identified hepatocellular damage. Histopathology demonstrated that APFO caused hepatocellular glycogen loss, hypertrophy, and hyperplasia. The hypertrophy was characterized by increased cyanide-insensitive palmitoyl CoA oxidation (a marker of peroxisome proliferation) and the induction of cytochrome P450 CYP4A1 (accompanied by smooth endoplasmic reticulum proliferation).

K2

This study investigated the PFOA-induced hepatomegaly in male rats.

Only data from study 1 are presented here but data from study 2 are similar.

Only two dose groups were used i.e. control and single treatment group and only male animals were used.

All authors represent organizations that have a current or former financial interest in ammonium perfluorooctanoate. Some authors are affiliated to 3M Company.

PFOA

CAS No. not given

Purity not given.

Kawashima et al. (1995)

Wistar rats

Male

4/dose.

0, 0.0025, 0.005, 0.01, 0.02 or 0.04% equivalent to 0, 3, 6, 12, 24 or 48**, 

i.p.

5 days,

Non-GL study.

GLP not stated.

NR

Males:

↑ acyl transferase activity (data only reported in figures).

↓ GSH S-transferase (data only reported in figures).

↑ TG (data only reported in figures).

Recovery not assessed.

Males:

NA / 3*

Morphological studies demonstrated that the administration of PFOA resulted in a marked proliferation of peroxisomes in hepatocytes.

PFOA produced tri-acylglycerol and cholesterol accumulation in liver. This seems inconsistent with the marked inductions of both peroxisome proliferation and peroxisomal & oxidation.

K2

This was a comparative study investigating hepatic responses following PFOA and PFDA exposure.

i.p. route of exposure was used.

Only male animals were used.

Study was funded by Ministry of Education, Science and Culture in Japan.