Per- and polyfluoroalkyl substances: evaluation of liver effects using in vivo data - PFAS/2023/06

Table 1 Lowest POD for PFAS based on liver effects - PFCAs

PFAS/2023/06

Last updated: 25 September 2025

This is a paper for discussion. This does not represent the views of the Committee and should not be cited.

*Derived by contractor; NA – not applicable. 

Substance / reference / table 

Sex, strain and species (Duration) 

NOAEL/LOAEL mg/kg bw/day 

Effect at LOAEL 

PFBA 

Butenhoff et al. (2012a) 

Table 7 

Male and female Sprague-Dawley rats, 

90 days. 

Recovery group: 3 weeks. 

Males: 6 / 30. 

Recovery 

30 / NA*. 

 

↑ absolute liver weight  

↑ ALP  

↓ TP  

↓ bilirubin  

↑ hepatocellular hypertrophy 

↑ mRNA of Acox, UGT1A1, CYP4A1, malic enzyme and Por  

↓ mRNA for Cyp1A1 in liver. 

Recovery:  

Absolute liver weight, TP, bilirubin and hepatocellular hypertrophy comparable to controls. 

PFHxA 

Loveless et al. (2009) 

Table 8 

Male and female Crl:Cd Sprague-Dawley rats, 

28 days. 

Recovery group: 30 and 90 days. 

Males: NA / 20. 

↑ ALT  

PFOA 

Guo et al. (2019)  

Table 9 

Male Balb/c mice,  

28 days. 

Recovery not assessed. 

Males: NA / 0.4. 

↑ relative liver weight, 

↑ TP 

↑ albumin 

↑ globulin 

↑ hepatocellular hypertrophy. 

PFNA 

Hadrup et al. (2016) 

Table 10 

Male Wistar rats, 

14 days. 

Recovery not assessed. 

Males: 0.25 / 5. 

↓ mRNA of AKR1C1, Ugt 2B15, Cyp2C11, Cyp1A2 and Cyp2B6. 

PFDA 

Frawley et al. (2018) Table 11 

Female Sprague-Dawley rats, 

28 days. 

Recovery not assessed. 

Females: NA / 0.125. 

↑ relative liver weight. 

PFUnDA 

Takahashi et al. (2014) 

Table 12 

Crl:CD (SD) rats,  

41-46 days, 

Recovery not assessed, 

Males and females: 0.1 / 0.3, 

 

Males 

↑ relative liver weight  

↓ total cholesterol  

↑ albumin/globulin ratio 

↑ hepatocyte centrilobular hypertrophy, 

Females:  

↓ total cholesterol  

↑ hepatocyte centrilobular hypertrophy, 

PFDoDA 

Kato et al. (2014) 

Table 13 

Male and female Crl:CD (SD) rats,  

42 days (males), 

41-46 days (females), 

Males and females: 0.1 / 0.5, 

 

Males 

↑ relative liver weight  

↑ ALP  

↓ total cholesterol. 

Females:   

↑ albumin/globulin ratio 

↑ relative liver weight  

↑ focal necrosis. 

PFTeDA 

Hirata-Koizumi (2015) 

Table 14 

Male and female Crl:CD (SD) rats,  

Males: 42 days beginning 14 days prior mating. 

Females: 14 days prior to mating, gestation and to PND5. 

 

Males:  1 / 3. 

↑ absolute liver weight  

↑ relative liver weight  

↑ centrilobular liver hypertrophy and steatosis. 

PFHxDA 

Hirata-Koizumi (2015) 

Table 15 

Male and female Crl:CD (SD) rats  

Males: 42 days beginning 14 days prior mating. 

Females: 14 days prior to mating, gestation and to PND5. 

Males and females: 20 / 100.  

 

↓ body weight 

↑ absolute liver weight 

↑ relative liver weight  

↑ centrilobular liver hypertrophy. 

Females: 

↑ centrilobular liver hypertrophy. 

PFODA 

(Hirata-Koizumi et al., 2012) 

Table 16 

Male and female Crl:CD (SD) rats  

Males: 42 days beginning 14 days prior mating. 

Females: 14 days prior to mating, gestation and to PND5. 

Males and females: 40 / 200. 

Males 

↑ absolute liver weight 

↑ relative liver weight  

↑ centrilobular hypertrophy. 

Females  

↑ relative liver weight.