Table 17

PFBS (potassium salt)

CAS no. Not given

98.2%.

Bijland et al. (2011)

APOE*3-Leiden.CETP mice.

Male,

6-8/dose.

0 or 0.03% in diet equivalent to 30.

Diet (vehicle).

Diet,

4-6 weeks,

OECD 407,

GLP not stated.

At 30 mg/kg bw/day at 4-6 weeks (mean ± SD)

Serum: 32.7-37.8 ± 6.6-10.2.

Males:

↓ plasma TG (data only reported in figures).

Altered gene expression related to lipolysis, fatty acid uptake and transport, fatty acid binding and activation, fatty acid oxidation and VLDL assembly.

Recovery not assessed.

Males:

NA / 30

The potency of PFAS to affect lipoprotein metabolism increased with increasing alkyl chain length, with PFBS having negligible effects on hepatic steatosis and hypolipidemia.

K2

This study investigated the mechanism underlying the effect of PFAS on lipoprotein metabolism.

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

The study was funded by the Nutrigenomics Consortium/Top Institute Food and Nutrition; the Netherlands Genomics Initiative; the Netherlands Organization for Health Care Research Medical Sciences); the Netherlands Organization for Scientific Research; the Netherlands Heart Foundation. Authors are affiliated to 3M company.

PFBS (potassium salt)

CAS No. 29420-49-3

98%.

Chen et al. (2022)

C57BL/6 mice.

Male 

6/dose.

0, 10 or 500 µg/l in drinking water equivalent to 2 or 104.

Drinking water (vehicle).

Drinking water.

28 days.

OECD 407.

GLP not stated.

At 2 mg/kg bw/day (mean ± SE)

Liver: 0.017 ± 0.008.

At 104 mg/kg bw/day

Liver: 0.027 ± 0.004.

Males:

↑ apoptosis (data only reported in figures).

↓ CAT activity (data only reported in figures).

Changes in hepatic lipidome (data only reported in figures; 238 lipids changed).

Recovery not assessed.

Males:

2 / 104

Toxicity in mouse liver occurred by inhibiting antioxidant enzyme activity, increasing sphingomyelins and phosphatidylcholines levels, and decreasing phosphatidylinositols levels.

K2

This study examined the potential health risks of low-dose PFBS and PFOS on lipid homeostasis in mouse liver.

Only three dose groups were used i.e., control and two treatment groups and only male animals were used.

This study was supported by the Natural Science Foundation of Jiangsu Province, and the Fundamental Research Funds for the Central Universities, the Research Program of State Key Laboratory of Pollution Control and Resource Reuse, and the Excellent Research Program of Nanjing University.

PFBS (potassium salt)

CAS no. Not given

98.2%.

Lieder et al. (2009a)

CRl:CD (SD) IGS BR VAF/PlusTM rats.

Male and female

10/sex/dose.

0, 60, 200 or 600.

Gavage,

Carboxymethylcellulose

90 days.

OECD 408

GLP study.

NR

Males:

No effects on liver reported.

Females:

No effects on liver reported.

Recovery not assessed.

Males:

600 / NA.

Females:

600 / NA. 

No specific comments on liver toxicity.

K1

This study investigated the toxicity of PFBS following a 90-day exposure.

No liver toxicity was noted.

Authors are affiliated to 3M Company. The 3M Company funded all aspects of the work.

PFBS (potassium salt)

CAS no. Not given

97.9%.

Lieder et al. (2009b)

CRl:CD (SD) IGS BR. VAF/PlusTM rats.

Male and female

30/sex/dose.

0, 30, 100, 300 or 1000

Gavage.

Carboxymethylcellulose

10 weeks.

OECD 416.

GLP not stated.

NR

Males (mean ± SD):

↑ absolute liver weight (g): 19.2 ± 2.4 vs 21.5 ± 2.9.

↑ relative liver weight (%): 3.4 ± 0.3 vs 3.8 ± 0.3.

↑ hepatocellular hypertrophy: 0 vs 3.

Females:

No effects on liver reported.

Recovery not assessed.

Males:

100 / 300.

Females:

1000 / NA*.

The F0 paternal NOAEL was 100 mg/kg bw/day due to hepatocellular hypertrophy and liver weight increase.

K1

This study investigated reproductive toxicity of PFBS in a two-generation study.

Liver weight was not measured in females. Limited liver-related endpoints were measured.

Authors are affiliated to 3M Company, a manufacture of PFBS. The funding for the study was provided by 3M Company.

PFBS

CAS No. 29420-49-3

>97%.

NICNAS. (2005)

Sprague-Dawley rats.

Male and female.

10/ sex/dose.

0, 100, 300 or 900.

Gavage,

Carboxymethylcellulose,

28 days,

OECD 407,

GLP study.

Recovery,

0 and 900,

14 days.

NR

Males (mean ± SE):

↑ absolute liver weight: 25% increase (quantitative data not reported).

↑ relative liver weight: 30% increase (quantitative data not reported).

Females:

No effects on liver reported.

Recovery

Liver weight comparable to controls.

Males:

300 / 900.

Females:

900 / NA*.

Liver weight findings were not observed in the recovery animals. These changes appear to be associated with the test material. The biological and toxicological significance of these observations is unclear due to the lack of supportive or histopathological findings. However, the liver and kidney may be seen as the potential target organs for toxicity and suggests liver weight changes are relevant.

K2

This study investigated the toxicity of PFBS following a 28-day exposure. 

Limited data were presented. Despite reservations by the author, the NOAEL was based on increased liver and kidney weight.

The study was funded by Australian Government Department of Health and Ageing, NICNAS.

PFBS

29420-49-3

>98%.

NICNAS. (2005)

Crl:CDv(SD)

IGS BR VAF/Plusv rats.

Male and female,

10/ sex/dose.

0, 60, 200 or 600

Gavage.

Carboxymethylcellulose

90 days,

OECD 408,

GLP study.

NR

Males (mean ± SEM):

No effects on liver reported.

Females:

↑ TP: 7% decrease (quantitative data not reported).

↑ albumin: 10% decrease (quantitative data not reported).

Recovery not assessed.

Males:

600 / NA*.

Females: 200 / 600*.

No specific comments on liver toxicity.

K2

This study investigated the toxicity of PFBS following a 90-day exposure.

Limited data were presented.

The study was funded by Australian Government Department of Health and Ageing, NICNAS.

PFBS

CAS no. 375-73-5

>97%.

NTP. (2022a)

Sprague-Dawley rats.

Male and female.

10/sex/dose.

0, 62.6, 125, 250, 500 or 1000.

Gavage,

2% Tween® 80

28 days,

NTP protocol,

GLP study (FDA GLP Regs).

At 62.6 mg/kg bw/day in males (mean ± SE),

Plasma: 2.2 ± 4.8,

Liver: 1.3 ± 0.2.

At 62.6 mg/kg bw/day in females.

Plasma: 0.2 ± 0.05

Liver: NR.

At 125 mg/kg bw/day in females,

Plasma: 0.31 ± 0.09

Liver: NR.

Males (mean ± SE):

↑ relative liver weight (mg/g body weight): 35.2 ± 0.79 vs 39.90 ± 0.48.

↓ TP (g/dL): 6.6 ± 0.0 vs 6.4 ± 0.1.

↓ globulin (g/dL): 2.3 ± 0.00 2.3 ±0.1.

↓ cholesterol (mg/dL): 133 ± 6 vs 110 ± 4.

↑ gene expression of Cyp4a1: 1.12 ± 0.17 vs 2.83 ± 0.49.

↑ gene expression of Cyp2b1:1.59 ± 0.41 vs 11.66 ± 2.78.

↑ gene expression of Cyp2b2: 1.27 ± 0.25 vs 7.72 ± 1.42.

Females:

↑ relative liver weight (mg/g body weight): 33.83 ± 0.90 vs 36.46 ± 0.50.

↑ gene expression of Cyp4a1:1.10 ± 0.18 vs 1.84 ± 0.29.

↑ gene expression of Cyp2b1: 1.51 ± 0.42 vs 152.85 ± 27.72.

↑ gene expression of Cyp2b2:1.89 ± 0.75 vs 81.44 ± 15.88.

Recovery not assessed.

Males:

NA / 62.6.

Females: 62.6 / 125.

A major target organ for PFBS was the liver.

The organ weight changes in liver appeared to correlate with histopathologic changes observed in the liver.

Hepatocyte hypertrophy observed with PFAS is likely due to the peroxisome proliferation. This is also supported by the elevated Acox1 and Cyp4a1 levels known to be inducible by PPARα agonists. Hepatocyte hypertrophy can also partially be mediated through CAR, because CAR-activated Cyp2b1 is also elevated.

Increases in serum biomarkers associated with hepatobiliary injury were also observed as well as decreases in cholesterol and TG.

K1

This study investigated the toxicity of PFBS following a 28-day exposure.

Liver enzymes were elevated only at higher doses than the LOAEL.

Although authors noted that liver weight changes correlated with hisopathologic changes, results show that hepatocyte hypertrophy occurred at higher doses than the LOAEL.

This study was funded by NTP. The study was audited retrospectively by an independent QA contractor.