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PFAS/2023/06 - Annex A

Table 5

PFAS/2023/06 Annex A

Last updated: 30 September 2025

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

Table 5. Acute toxicity studies for PFCAs – PFDA

*Derived by contractor; ** calculated according to EFSA. (2012); NR – not reported; NA – not applicable.

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. not given

Purity not given.

Adinehzadeh et al. (1999)

F-344 rats

Male

4-5.

0, 5, 15 or 25

Propyleneglycol:water

i.p.

Single dose,

Non-GL study,

GLP not stated.

NR

Males:

↑ fatty acyl-Co A oxidase activity (data only reported in figures).

Recovery not assessed.

 

 

Males:

NA / 5*

PFDA produces hepatotoxic effects in rats that are dose-dependent in the range 2±50 mg/kg by single injection i.p.

 

K2

This study hypothesised that the metabolic effects of PFDA on hepatic phosphocholine content are not due to toxicity but demonstrate a distinct response to PFDA treatment.

i.p. route of exposure was used.

Only 4-5 male animals were used.

Study was funded by Air Force Office of Scientific Research, Air Force Systems Command, USA.

PFDA

CAS No. not given

Purity not given.

Adinehzadeh et al. (1999)

F-344 rats

Male

5-6.

0, 15 or 50

Propyleneglycol:water

i.p.

Single dose,

Non-GL study,

GLP not stated.

NR

Males (mean ± SE):

↑ total lipids (mg/g liver): 54.6 ± 4.2 vs 37.1 ± 1.7,

↑ phosphatidylcholine (µmol/g liver): 34.0 ± 3.4 vs 26.5 ± 1.4),

↑ phosphatidylethanolamine:

12.6 ± 1.3 vs 9.6 ± 0.4.

Recovery not assessed.

 

Males:

NA / 15*

PFDA produces hepatotoxic effects in rats that are dose-dependent in the range by single injection i.p.

PFDA produces similar effects on hepatic phospholipid metabolism at 15 and 50 mg/kg. Such effects are characterized by significant increases in liver phosphatidylcholine and phosphatidylethanolamine content.

K2

This study hypothesised that the metabolic effects of PFDA on hepatic phosphocholine content are not due to toxicity but demonstrated a distinct response to PFDA treatment.

i.p. route of exposure was used.

Only 4-5 male animals were used.

Study was funded by Air Force Office of Scientific Research, Air Force Systems Command, USA.

PFDA

CAS No. not given

96%.

Cheng and Klaassen (2008)

C57BL/6 mice

Male

4/dose.

0, 0.5, 1.0, 10, 20, 40 or 80, Propyleneglycol:water

i.p.

Single dose,

Non-GL study,

GLP not stated.

NR

Males:

↑ mRNA of cyp4A14 (data only reported in figures).

Recovery not assessed.

Males:

1 / 10*

Relatively low doses of PFDA activates PPAR-α, and thus increases Cyp4A14 expression. In contrast, at high doses. (>10mg/kg), PFDA activates both CAR and PPAR-α nuclear receptors, and increases the expression of Cyp2B10 and 4A14, respectively. Therefore, PPAR-α and CAR play central roles in regulating mouse Cyps by PFDA.

K2

This study investigated if expression of cytochrome P450 was 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.

PFDA

CAS No. not given

96%.

Cheng and Klaassen (2008)

C57BL/6 mice

Male

5/dose.

0 or 80

Propyleneglycol:water

i.p.

Single dose,

Non-GL study,

GLP not stated.

NR

Males:

↑ mRNA of Cyp2B10,

3A11 and 4A14

↑ protein levels of Cyp2B and 4A (data only reported in figures).

Recovery not assessed.

Males:

NA / 80*

PFDA increases 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.

PFDA

CAS No. not given

Purity not given.

Kawashima et al. (1995)  

Wistar rats

Male

4/dose.

0, 0.00125, 0.0025, 0.005 or 0.01% equivalent to 0, 1.5, 3, 6 or 12**,

i.p.

5 days.

NR

Males:

↑ relative liver weight (data only reported in figures)

↑ acyltranserase activity (data only reported in figures)

↑ TG (data only reported in figures).

Recovery not assessed.

Males:

NA / 1.5*

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

PFDA produced triacylglycerol and cholesterol accumulation in liver. This seems inconsistent with the marked inductions of both peroxisome proliferation and peroxisomal & oxidation. These findings suggest that the pattern of toxicity produced by PFDA differs from that produced by PFOA, and that PFDA is more toxic to hepatocytes than PFOA.

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, Japan.
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