Tetraethylammonium heptadecafluorooctanesulphonate

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: short-term oral

Type of information:

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

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented and scientifically acceptable

Data source

Reference

Reference Type:

publication

Title:

Gestational and lactational exposure to potassium perfluorooctanesulfonate (K+PFOS) in rats: Developmental neurotoxicity

Author:

Butenhoff JL, Ehresman DJ, Chang SC, Parker GA, Stump DG

Year:

2009

Bibliographic source:

Reprod Toxicol 27, 319-330

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 426 (Developmental Neurotoxicity Study)

Principles of method if other than guideline:

examination of developmental neurotoxicity

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Potassium heptadecafluorooctane-1-sulphonate

EC Number:

220-527-1

EC Name:

Potassium heptadecafluorooctane-1-sulphonate

Cas Number:

2795-39-3

IUPAC Name:

potassium 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluorooctane-1-sulfonate

Details on test material:

K+PFOS (lot no. 217. 86 9% purity) was provided by 3M Company (Sr Paul. MN).

Test animals

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 05% Tween® 20

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Doses were given once daily from GD 0 to PND 20 for the main study phase rats and from GD 0 to GD 19 for the satellite phase rats

Frequency of treatment:

once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.1, 03, and 10 mg/kg-d
Basis:
nominal conc.

No. of animals per sex per dose:

4 groups of 2 dose-groups in the main study
An additional 10 mated females were assigned as satellite phase rats to each of the 4 groups

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

0.3 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Remarks on result:

other: Generation: maternal (migrated information)

2

Dose descriptor:

NOAEL

Effect level:

0.3 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Remarks on result:

other: Generation: offspring (migrated information)

Any other information on results incl. tables

No significant effect was noted on maternal health or reproductive outcomes from dosing of maternal rats with K+PFOS throughout gestation. Maternal body weights were statistically significantly lower in the 1.0 mg/kg-d dosage group from PND 4 through the end oflactation. Offspring fram K+PFOS-treated maternal graups did not differ significantly from controls with respect to birth weight. growth, age and weight at attainment of sexual maturation, learning and memory, acoustic startle, various behavioral endpoints, and brain weight. Male offspring from the 1.0 mg/kg-d maternal treatment group displayed increased motor activity and reduced habituation on PND 17 but not on PND 13, 21, and 61. The maternal no-observed-adverse-effect-level (NOAEL) was 0.3 mg/kg-d based on decreased body weights observed in lactation. The maternal dose associated with the NOAEL for male offspring was 0.3 mg/kg-d based on increased motor activity and reduced habituation in the 1.0 mg/kg-d maternal dose-group male offspring on PND 17. The maternal dose associated with the NOAEL for female offspring was > 1.0 mg/kg-d.

Applicant's summary and conclusion

Executive summary:

The objective of this study was to evaluate the functional and morphological changes to the nervous system in rats having gestational and lactational exposures to PFOS per current test guidelines (EPA OPPTS 870.6300 and OECD 426). Female SD rats (25/dosage group) were given daily oral doses of either 0.0, 01, 0.3, or 1.0 mg/kg-d potassium PFOS (K+PFOS) from gestation

day (GD) 0 through postnatal day (PND) 20. Offspring were observed through PND 72 for growth, maturation, motor activity, learning and memory, acoustic startle reflex, various behavioral manifestations, and brain weight. Specimens were taken from dams, fetuses, and pups for serum and tissue PFOS concentration, thyroid status end points, and liver mRNA transcript analysis. No significant effect was noted on maternal health or reproductive outcomes from dosing of maternal rats with K+PFOS throughout gestation. Maternal body weights were statistically significantly lower in the 1.0 mg/kg-d dosage group from PND 4 through the end of lactation. Offspring from K+PFOS-treated maternal graups did not differ significantly from contrals with respect to birth weight.

growth, age and weight at attainment of sexual maturation,learning and memory, acoustic startle, various behavioral endpoints, and brain weight. Male offspring from the 1.0 mg/kg-d maternal treatment group displayed increased motor activity and reduced habituation on PND 17 but not on PND 13, 21, and 61. The maternal no-observed-adverse-effect-Ievel (NOAEL) was 0.3 mg/kg-d based on decreased body weights observed in lactation. The maternal dose associated with the NOAEL for male offspring was 0.3 mg/kg-d based on increased motor activity and reduced habituation in the 1.0 mg/kg-d maternal dose-group male offspring on PND 17. The maternal dose associated with the NOAEL for female offspring was> 1.0 mg/kg-d. Mean serum concentrations of PFOS are several hundred times higher than those reported for females in the Uni ted States general population.