Heptadecafluorooctanesulphonyl fluoride

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The experimental study is referred to PFOS (Potassium Perfluorooctane sulfonic acid). The substance RM90 is a salt of PFOS.

Data source

Reference

Reference Type:

publication

Title:

ENVIRONMENTAL AND HEALTH ASSESSMENT OF PERFLUOROOCTANE SULFONIC ACID AND ITS SALTS

Author:

3M

Bibliographic source:

Various sources listed in the assessment report.

Report date:

2003

Materials and methods

Test guideline

Guideline:

other: not known

Principles of method if other than guideline:

Method not available in the pubblication.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Heptadecafluorooctane-1-sulphonic acid

EC Number:

217-179-8

EC Name:

Heptadecafluorooctane-1-sulphonic acid

Cas Number:

1763-23-1

IUPAC Name:

1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluorooctane-1-sulfonic acid

Test animals

Species:

other: rats and rabbits

Strain:

not specified

Details on test animals or test system and environmental conditions:

Pregnant rats and rabbits on prenatal development of their embryos and fetuses.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Results and discussion

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
PFOS caused maternal and fetal toxicity. Initial studies with PFOS reported a lesion in the lens of the eye in all treated groups. The study director subsequently retracted the causal association between this effect and chemical exposurwhen it was established that the “lesion” was an artifact associated with the method of free-hansectioning used in the fetal examination. These lesions were not observed in a repeat study in same laboratory that conducted the original study.
Since those original studies were conducted, additional prenatal developmental toxicity studiehave been performed in the rat and rabbit (Case et al., 2001a).
Results in the three PFOS studies were similar. Maternal toxicity and developmental toxicity were expressed as reductions in maternal weight gain or fetal body weight. Reductions in food consumption commonly paralleled the effect on maternal weight. Fetal effects were primarily associated with maturational delays, e.g., skeletal variations and delayed ossification. Abortions were observed in rabbits at a dose of 2.5 mg/kg and higher. The lowest developmental toxicity NOAEL for rat and rabbit were the same, 1 mg/kg body weight. The maternal toxicity NOAEL was 0.1 and 1.0 mg/kg for rabbit and rat, respectively. Fetal toxicity, rather than anatomical malformations, characterized the principal effectof PFOS. Developmental effects were seen only in conjunction with maternal toxicity, indicating that PFOS is not a selective developmental toxicant.
In a recent study, findings of cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium were found in rat and mouse fetuses, primarily at maternal doses of 10 and 20 mg/kg/day, respectively (Thibodeaux et al., 2003). In these studies, pregnant rats were given doses of 1,2, 3, 5,or 10 mg/k ay from gestational day (GD) 2 through GD 20, and pregnant CD-1 mice were given 1, 5, 10, 15, and 20mg/kg/day from GD 1 through GD 17. Maternal weight gains and serum triglycerides were reduced in a dose-dependent manner in both species, and pregnant mice experienced marked liver enlargement at 10, 15, and 20 mg/kg/day dose levels. The numbers of implantation sites and live fetuses at birth were not altered as compared to controls; however, fetal weight in the rats was slightly reduced. The birth defects that occurred were at doses that produced significant maternal toxicity.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Design	NOAEL (mg/kg)	LOAEL (mg/kg)	Effects
Rat SD, Group size: 22;Dose (a): 0, 1, 5, 10	Maternal 5; Development 10	Maternal 10; Development none	Maternal Body weight
Rat SD; Group size: 25; Dose (a): 0, 1, 5, 10	Maternal 1; Development 1	Maternal 5; Development 5	Maternal Body weight; Clinical signs g.i. lesions. Dev. Body wt, visc, anom, skel. var.
Rabbit NZW; Group size: 22; Dose (a): 0,0.1, 1, 2.5, 3.75	Maternal 0.1; Development 1	Maternal1; Development 2.5	Maternal body weight, abortionsDev. Body wt., delayed ossification