Table 11

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

PFDA

CAS No. 335-76-2

97.8%.

Frawley et al. (2018)

Sprague-Dawley rats.

Female 8/group.

0, 0.125, 0.25, 0.5, 1 or 2.

Deionized water/2%, Tween 80,

Gavage,

28 days,

Non-GL study,

GLP not stated.

NR

Males (mean ± SE):

↑ relative liver weight (%): 3.42 ± 0.09 vs 3.77 ± 0.10.

Recovery not assessed.

Females:

NA / 0.125

The data suggest that, under conditions that do not induce acute toxicity, exposure to PFDA, a long chain polyfluoroalkylcompound, may induce adverse effects that are consistent with the PFAS class.

K2

This project investigated the hepatotoxicity and immunotoxicity of PFDA due to the structural similarity to other PFAS.

Only liver weight was measured despite the title indicating hepatotoxicity was assessed.

This research was supported by the NIH, National Institute of Environmental Health Sciences, NTP Contract, the NTP Statistical Support Contract, and the NTP Chemistry Support Services Contract.

PFDA

CAS No. 335-76-2

97.8%.

Frawley et al. (2018)

B6C3F1 mice,

Female

8/group.

0, 0.31, 0.625, 1.125, 2.5 or 5. 

Deionized water/2%, Tween 80,

Gavage,

28 days,

Non-GL study,

GLP not stated.

NR

Males (mean ± SE):

↑ absolute liver weight (g): 1.122 ± 0.031 vs 1.42 ± 0.054

↑ relative liver weight (%): 4.83 ± 0.08 vs 5.61 ± 0.06.

Recovery not assessed.

Females: 0.31 / 0.625.

The data suggest that, under conditions that do not induce acute toxicity, exposure to PFDA, a long chain polyfluoroalkylcompound, may induce adverse effects that are consistent with the PFAS class.

K2

This project investigated the hepatotoxicity and immunotoxicity of PFDA due to the structural similarity to other PFAS.

Only liver weight was measured despite the title indicating hepatotoxicity was assessed.

This research was supported by the NIH, National Institute of Environmental Health Sciences, NTP Contract, the NTP Statistical Support Contract, and the NTP Chemistry Support Services Contract.

PFDA

CAS No. 335-76-2

>97%.

NTP. (2022b)

Sprague-Dawley rats.

Male and female. 10/sex/dose.

0, 0.156. 0.312. 0.625. 1.25 or 2.5. 

Tween® 80 in deionized water.

Gavage,

28 days,

NTP protocol,

GLP study.

At 0 mg/kg bw/day in males (mean ± SE).

Plasma: 0.022 ± 0.004

Liver: <LOD.

At 0.156 mg/kg bw/day in males.

Plasma: 8.5 ± 0.6

Liver: 44.7 ± 1.5.

At 0 mg/kg bw/day in females.

Plasma: 0.042 ± 0.017

Liver: not measured.

At 0.156 mg/kg bw/day in females.

Plasma:11.2 ± 0.4.

Males (mean ± SD):

↑ absolute liver weight (g): 11.89 ± 0.51 vs 13.54 ± 0.40.

↑ relative liver weight (g): 35.50 ± 0.97 vs 39.32 ± 0.53.

↓ TP (g/dL): 6.4 ± 0.1 vs 6.2 ± 0.1.

↓ globulin (g/dL): 2.2 ± 0.1 vs 1.9 ± 0.0.

↑ albumin/globulin ratio: 1.9 ± 0.1 vs 2.2 ± 0.1.

↓ cholesterol (mg/dL): 107 ± 5 vs 78 ± 3.

↑ gene expression of Acox1: 1.03 ± 0.10 vs 1.70 ± 0.17.

↑ gene expression of Cyp4a1: 1.04 ± 0.10 vs 10.85 ± 1.11.

↑ gene expression of Cyp2b1: 1.06 ± 0.21 vs 3.33 ± 0.57.

↑ gene expression of Cyp2b2: 1.00 ± 0.13 vs 4.24 ± 0.52.

Females (mean ± SD):

↑ absolute liver weight (g): 7.63 ± 0.28 vs 8.94 ± 0.36.

↑ relative liver weight (g): 33.52 ± 0.75 vs 37.66 ± 0.89.

↑ albumin/globulin ratio: 2.4 ± 0.1 vs 2.8 ± 0.1.

↑ gene expression of Acox1: 1.06 ± 0.12 vs 1.58 ± 0.12.

↑ gene expression of Cyp2b1: 1.44 ± 0.37 vs 14.39 ± 4.01.

↑ gene expression of Cyp2b2: 1.47 ± 0.42 vs 12.28 ± 2.95.

Recovery not assessed.

Males:

NA / 0.156.

Females:

NA / 0.156.

A major target organ of toxicity for PFDA was the liver.

Cyp2b1/Cyp2b2 activation indicates CAR-mediated activity, and Acox1/Cyp4a1 activation suggests PPAR-α activity.

PFHxA is the most potent for Cyp induction.

PFAS administration increased the levels of serum biomarkers associated with hepatobiliary injury.

K1

This study investigated toxicity of a number of PFAS, including PFHxA, following a 28-day exposure.

No treatment-related clinical observations were reported.

Plasma concentrations of PFDA increased with increasing dose in both males and females and were marginally higher in females (30% or less) compared to males across the corresponding dose groups. Liver concentrations of PFDA were measured in males only and increased with dose, but when normalized to dose, liver concentrations decreased with increasing dose.

Government funded study. Study was audited retrospectively by an independent QA contractor.