Table 21

Substance / CAS no. / purity / reference

Strain & species / sex / no. of animals

Dose (mg/kg bw/day) / vehicle / route of admin / duration / Guideline (GL) study / Good Laboratory Practice (GLP) status

PFAS concentration (µg/mL / µg/g)

Observed effects at LOAEL (controls vs treated groups).

Recovery (controls vs treated groups).

Published NOAEL / LOAEL (mg/kg bw/day)

Study author comments

Comments

PFOA (ammonium salt)

CAS No. 3825-26-1

98.4%.

Xu et al. (2022)

Balb/c mice. Pregnant females. 8/dose.

0 or 1,

Milli Q water,

Gavage,

GD0 to parturition,

Non-GL study,

GLP not stated.

NR

Females (mean ± SD):

↑ absolute and relative liver weight: data only provided in figures.

↑ AST and ALT: data only provided in figures.

Hepatocyte hypertrophy, disarrangement, cytoplasmic loss, nuclear migration, acidophil bodies and inflammatory cell infiltration.

↑ mRNA levels of genes related to inflammation: Tlr4, Myd88, Traf6, Rela, IL1b and Tnf.

↑ apoptosis in liver: protein expression of PARP-1, cleaved caspase-3 and Bax.

Recovery not assessed.

Females:

NA / 1*

Histopathological changes, characterized by enlargement and disarrangement of hepatocytes, cytoplasm loss, nuclear migration, acidophilbodies, inflammatory cell infiltration, and reduction of glycogen storage, were observed in maternal mice in the PFOA exposed groups. Serum ALT and AST were also significantly increased.

Gestational exposure to PFOA induced maternal hepatic alterations through the gut-liver axis.

K2

This was a comparative study investigating the mechanisms of maternal hepatotoxicity between PFOA and GenX.

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

PFOA

CAS No. not given

99.2%.

Zhang et al. (2021)

Kunming mice. Pregnant females, 10/dose.

0, 1, 5, 10, 20 or 40

Distilled water,

Gavage,

GD1-7,

Non-GL study,

GLP not stated.

NR

Males (mean ± SD):

↑ liver index: data only provided in figures.

↓ SOD and GSH-Px in liver: data only provided in figures

↑ MDA in liver: data only provided in figures.

Recovery not assessed.

Females:

NA / 1*

The present study results suggest that PFOA is hepatotoxic in a dose-dependent manner, and short-term exposure can cause swelling of the liver cells, which explains the increase in liver index.

The higher the PFOA levels administered, the lower the SOD and GSH-Px, and the greater the MDA accumulation. The results suggested that oxidative damage is the potential mechanism of PFOA hepatotoxicity.

K1

This study investigated the mechanism of PFOA toxicity on the liver of mice during early pregnancy.

No change in body weight was reported. Histopathological changes were only seen at the higher doses.

The study was financially supported by the National Natural Science Foundation of China.