Tetraethylammonium heptadecafluorooctanesulphonate

Specific investigations: other studies

Administrative data

Endpoint:

endocrine system modulation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented and scientifically acceptable

Data source

Reference

Reference Type:

publication

Title:

Neuroendocrine effects of perfluorooctane sulfonate in rats

Author:

Austin M, Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SMJ

Year:

2003

Bibliographic source:

Environ Health Perspect 111, 1485-1489

Materials and methods

Principles of method if other than guideline:

In this study, adult female rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg body weight (BW) for 2 weeks. Food and water intake, BW, and estrous cycles were monitored daily. At the end of treatment, PFOS levels in tissues were measured by high-performance liquid chromatography (HPLC) interfaced with electrospray mass spectrometry. Changes in brain monoamines were measured by HPLC with electrochemical detection, and serum corticosterone and leptin were monitored using radioimmunoassay

GLP compliance:

no

Type of method:

in vivo

Endpoint addressed:

neurotoxicity

Test material

Test material information

Constituent 1

Reference substance name:

2795-23-1

IUPAC Name:

2795-23-1

Details on test material:

potassium salt of PFOS (> 96% purity; Tokyo Chemical Industries, Tokyo, Japan)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

DMSO

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Post exposure period:

none

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1 or 10 mg/kg bw
Basis:

No. of animals per sex per dose:

n = 8

Control animals:

yes, concurrent vehicle

Results and discussion

Details on results:

Accumulation of PFOS in tissues.
Although PFOS was not detectable in any of the tissues in control animals, there was a dose-dependent increase in the concentrations of PFOS in all of the tissues, including various parts of the brain from exposed rats. PFOS was also found in the brains of rats exposed to the lower dose.
Among the various parts of the brain, the hypothalamus of rats exposed to the higher dose had greater accumulation, with at least a 3-fold increase compared with other brain areas. However, PFOS was not detected in the hypothalamus of the rats exposed to the lower doses. Among various body tissues, the liver contained the highest concentration, followed by the kidney and serum.
Body weight.
There were no significant differences in BW among the treatment groups at the beginning of the experiment. BW (mean ± SE) in control animals on day 0 (pretreatment) was 233.5 ± 8.7 g and remained at about that level on day 14 (240.1 ± 8.2 g). In contrast, BW in animals treated with the high dose of PFOS (10 mg/kg of BW) was 235.9 ± 8 g on day 1 and decreased significantly to 208 ± 7.1 g by day 14 (p = 0.0039; F = 7.306; df = 2).
Treatment with the low dose of PFOS did not produce any significant change in BW throughout the treatment period.
Estrous cycles.
All the animals in the control group exhibited regular 4-day estrous cycles. In contrast, only about 66% of the animals were regular cyclers in the low-dose group. Treatment with the high dose of PFOS further reduced the number of regular cyclers to 42% and increased the number of animals in persistent diestrus from 8% in the low-dose group to 33%. There was a significant change in cyclicity between the control and high-dose group (p = 0.0442; df = 2).
Serum leptin.
At the end of treatment, the leptin level (mean ± SE; Figure 5) in the sera of control animals was 10.5 ± 1.5 ng/mL. Treatment with the low dose of PFOS did not produce any significant changes in serum leptin levels. In contrast, treatment with the high dose of PFOS resulted in a marked decrease in
serum leptin levels (1.5 ± 0.5 ng/mL; p = 0.0183; F = 5.399, df = 2).
Serum corticosterone.
The corticosterone level (mean ± SE; Figure 6) in the sera of control animals at the time of sacrifice was 332.6 ± 62.8 ng/mL. Treatment with the low
dose of PFOS did not affect serum corticosterone levels. In contrast, treatment with the high dose of PFOS significantly increased corticosterone levels by about 75% (p = 0.0256; F = 4.814, df = 2).
Monoamines in the hypothalamus.
Catecholamine concentrations in the PVN and the MPA are shown in Figure 7. The NE level (mean ± SE protein) in the PVN of control animals was 11.2 ± 1.6 pg/µg. The level was significantly higher (19.7 ± 1.6 pg/µg) in animals treated with the high dose of PFOS (p = 0.0413; F = 3.786, df = 2). Treatment with the low dose of PFOS did not affect NE concentrations in the PVN. Treatment with either the low dose or high dose of PFOS did not affect NE concentrations in the MPA. PFOS treatment did not affect DA concentrations in either the PVN or the MPA.

Any other information on results incl. tables

Treatment with PFOS produced a dose-dependent accumulation of this chemical in various body tissues, including the brain. PFOS exposure decreased food intake and BW in a dose-dependent manner. Treatment with PFOS affected estrous cyclicity and increased serum corticosterone levels while decreasing serum leptin concentrations. PFOS treatment also increased norepinephrine concentrations in the paraventricular nucleus of the hypothalamus. These results indicate that exposure to PFOS can affect the neuroendocrine system in rats.

Applicant's summary and conclusion

Executive summary:

In this study, adult female rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg body weight (BW) for 2 weeks. Food and water intake, BW, and estrous cycles were monitored daily. At the end of treatment, PFOS levels in tissues were measured by high-performance liquid chromatography (HPLC) interfaced with electrospray mass spectrometry. Changes in brain monoamines were measured by HPLC with electrochemical detection, and serum corticosterone and leptin were monitored using radioimmunoassay. Treatment with PFOS produced a dose-dependent accumulation of this chemical in various body tissues, including the brain. PFOS exposure decreased food intake and BW in a dose-dependent manner. Treatment with PFOS affected estrous cyclicity and increased serum corticosterone levels while decreasing serum leptin concentrations. PFOS treatment also increased norepinephrine concentrations in the paraventricular nucleus of the hypothalamus. These results indicate that exposure to PFOS can affect the neuroendocrine system in rats.