Tetraethylammonium heptadecafluorooctanesulphonate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented and scientifically acceptable

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. I: Maternal and prenatal evaluations

Author:

Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Barbee BD, Richards JH, Butenhoff JL, Stevenson LA, Lau C

Year:

2003

Bibliographic source:

Toxicol Sci 74, 369-381

Reference 2

Reference Type:

publication

Title:

Maternal and developmental toxicity of perfluorooctane sulfonate (PFOS) in the mouse

Author:

Thibodeaux J, Hanson RG, Grey RE, Barbee BD, Richards JH, Butenhoff JL, Rogers JM, Lau C

Year:

2003

Bibliographic source:

Toxicologist 72, Suppl 1, 342, Abstr No 1658

Materials and methods

Principles of method if other than guideline:

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3 -) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mglkg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1,5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehiele (1 ml/kg for rats and 10 ml/kg for mice). Maternal
weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined.

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:

Perfluorooctane sulfonate (PFOS, potassium salt; 91 % pure) was purchased from Fluka Chemical (Steinheim, Switzerland)

Test animals

Species:

other: rat + mouse

Strain:

other: Sprague-Dawley rats and CD-I mice

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% Tween-20

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

Timed-pregnant Sprague-Dawley rats and CD-I mice obtained from Charles River Laboratories (Raleigh, NC) were bred within a 4-h period and overnight, respectively.

Duration of treatment / exposure:

rats: from gestational day (GD) 2 to GD 20
mice: GD 1 to GD 17

Frequency of treatment:

daily

Duration of test:

rats were sacrificed on GD 21 and mice on GD 18

Doses / concentrations

Remarks:

Doses / Concentrations:
rats: 0, 1, 2, 3, 5, or 10 mg/kg; mice: 0, 1,5, 10, 15, and 20 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

no data

Control animals:

yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

1 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3,) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of

thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterollevels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively.

Applicant's summary and conclusion

Executive summary:

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3 -) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mglkg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1,5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehiele (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined.

Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3,) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterollevels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. The results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.