Table 8

PFHxA

CAS No. not given

98.5%.

Chengelis et al. (2009)

Sprague-Dawley rats

Male and female

10/sex/dose.

0, 10, 50 or 200,

Deionized water,

Gavage,

90 days,

Non-GL study,

GLP not stated.

Recovery group:

0 and 200,

28 days.

NR

Males (mean ± SD):

↓ body weight: data only provided in figures.

↓ cholesterol (mg/dL): 57 ± 12.5 vs 42 ± 9.4.

Females:

No adverse effects reported (NOAEL is highest dose tested).

Recovery:

Data not presented as animals only treated with 200 mg/kg bw/day and not 50 mg/kg bw/day (LOAEL).

Males:

10 / 50.

Females:

200 / NA*.

Effects seen typically suggest an impact on the liver, but the only histologic change in the liver was hepatocellular hypertrophy. This histologic change is considered an adaptive change and is not associated with the serum chemistry changes identified. In the absence of any correlating target organ changes, these slight clinical chemistry changes, while possibly related to PFHxA treatment, are of questionable toxicological significance.

K1

This study investigated the subchronic oral toxicity of PFHxA in rats following previous papers that showed PFHxA does not bioaccumulate and does not show a sex difference.

There were no treatment-related clinical observations or changes in organ weights or clinical chemistry apart from a decrease in cholesterol.

Decreases in body weight, whilst significantly different to controls at 50 mg/kg bw/day, did not show a dose response. The recovery group only consisted of animals treated with 0 or 200 mg/kg bw/day so no data are available regarding the reversibility of body weight at the LOAEL.

Authors are affiliated to AGC Chemicals. Study funding was not reported.

PFHxA

(sodium salt)
CAS No. 2923-26-4

100%.

Loveless et al. (2009)

Crl:CD Sprague-Dawley rats.

Male and female. 10/sex/dose.

0, 20, 100 or 500,

NANOpure® water.

Gavage.

92 days.

OECD 408.

GLP not stated.

Recovery group:

0 and 200.

10/sex/dose.

30 and 90 days.

NR

Males (mean ± SD):

↑ ALT (U/L): 27 ± 5 vs 63 ± 64.

Females: No adverse effects reported (NOAEL is highest dose tested).

Recovery:

Data not presented as animals only treated with 200 mg/kg bw/day and not 20 mg/kg bw/day (LOAEL).

Males:

NA / 20*.

Females:

500 / NA*.

Statistically significant differences from controls were observed for a number of parameters (e.g., AST, ALT, bilirubin, TP), particularly in males dosed with 500mg/kg, but these changes were considered non-adverse for a variety of reasons. Some of these reasons included low incidence, not occurring in a dose–response fashion, direction of change not associated with adversity, or the changes reflected adaptive responses following effects on the liver.

K1

The objective of this study was to investigate acute, repeat dose subchronic, one-generation reproduction, developmental toxicity of PFHxA.

The increase in ALT seen at the lowest dose tested is considered to be non-adverse and was comparable to controls after recovery. Other effects are seen at higher doses but are also considered to be non-adverse.

All authors are affiliated to the DuPont Company. Study funding was not reported.

PFHxA

Cas No. 307-24-4

>99%.

NTP. (2022b)

Sprague-Dawley rats

Male and female 10/sex/dose.

0, 62.6, 125, 250, 500 or 1000 (half doses administered twice daily).

Tween® 80 in deionized water,

Gavage,

28 days,

NTP protocol,

GLP study (FDA GLP, Regs).

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

Plasma: <LOD

Liver: <LOD.

At 62.6 mg/kg bw/day in males.

Plasma: 0.378 ± 0.178

Liver: <LOD.

At 0 mg/kg bw/day in females.

Plasma: <LOD.

Liver: not measured.

At 62.6 mg/kg bw/day in females.

Plasma: 0.129 ± 0.016.

Liver: not measured.

Males (mean ± SE):

↓ cholesterol (mg/dL): 126 ± 4 vs 101 ± 4.

↑ gene expression of Acox1:

↑ gene expression of Cyp4a1: 1.03 ± 0.09 vs 2.81 ± 0.33.

↑ gene expression of Cyp2b1: 1.29 ± 0.35 vs 2.65 ± 0.32.

↑ gene expression of Cyp2b2: 1.16 ± 0.20 vs 2.22 ± 0.25.

Females:

↑ gene expression of Cyp2b1: 1.83 ± 0.62 vs 4.66 ± 1.22.

↑ gene expression of Cyp2b2: 1.95 ± 0.72 vs 6.32 ± 1.32.

Recovery not assessed.

Males:

NA / 62.6*.

Females:

NA / 62.6*.

A major target organ of toxicity for PFHxA was the liver. Cyp2b1/Cyp2b2 activation indicates CAR-mediated activity, and Acox1/Cyp4a1 activation suggests PPAR-α activity.

PFHxA is the least potent for Cypinduction. This pattern of potency was also reflective of the changes in liver weight and the occurrences of hepatocellular hypertrophy.

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. Decreased body weight and changes in liver weight and clinical chemistry, apart from cholesterol, were only seen at higher doses.

PFHxA concentrations in liver were only measured in males and were only quantifiable in the 250-1000 mg/kg bw/day dose groups.

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