Tetraethylammonium heptadecafluorooctanesulphonate

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

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:

Cleft palate caused by perfluorooctane sulfonate is caused mainly by extrinsic factors

Author:

Era S, Harada KH, Toyoshima M, Inoue K, Minata M, Saito N, Takigawa T, Shiota K, Koizumi A

Year:

2009

Bibliographic source:

Toxicology 256, 42-47

Materials and methods

Principles of method if other than guideline:

Examination whether the concentration of PFOS in fetal serum was related to susceptibility to CP. The authors compared palatogenesis following the administration of various concentrations of PFOS to dams. Histological examination were conducted on gestational day (GD) 15 and 18, and alizarin red/alcian blue staining of fetal heads on GD18. Finally, cultured palatal shelves (PSs) of GD14 fetuses, which had not yet made contact with each other, for 48 h, were examine whether the shelves maintained the ability to fuse

GLP compliance:

no

Type of method:

in vivo

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:

PFOS potassium salt (FW 538.22; purity >98%; Fluka Chemical, Milwaukee, MI, USA) was used for all experiments

Test animals

Species:

mouse

Strain:

ICR

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% polyoxyethylene sorbitan monolaurate (Tween 20)

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

up to 18 days

Frequency of treatment:

daily

Duration of test:

up to 18 days

Doses / concentrations

Remarks:

Doses / Concentrations:
9, 13, 20 and 30 mg/kg or 20 and 50 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

no data

Control animals:

not specified

Results and discussion

Observed effects

The incidence of CP increased from 7.3% with a fetal serum concentration of PFOS of 110.7±13.4g/ml (13 mg/kg) to 78.3% with 138.6±0.9g/ml
(20 mg/kg). PFOS at 50 mg/kg on GD11–15 caused CP at a rate of 6.1%, meanwhile PFOS at 20 mg/kg on GD1–17 caused a CP rate of 89.3%. Failure of palatal shelf elevation was observed with 20 mg/kg PFOS. PFOS at 20 mg/kg on GD1–17 and 50 mg/kg on GD11–15 inhibited mandibular growth to the same extent, even though the rate of CP was different. Explants exposed to PFOS 20 mg/kg and Tween 20 showed 94% (34/36) and 100% (31/31) fusion, respectively. We demonstrated that increasing the oral dose of PFOS from 13 to 20 mg/kg resulted in a significant increase in CP even though there was only a small increase in serum concentration of PFOS. PFOS prevented elevation of the PSs above the tongue because their growth/fusion potentialwas maintained. Mandibular hypoplasia did not seem to play a critical role in the pathogenesis of CP.

Any other information on results incl. tables

CP induced by PFOS is the result of failure of PS elevation and a slight increase in serum concentration of PFOS resulted in dramatic increases in CP, suggesting a sharp threshold.

Applicant's summary and conclusion

Executive summary:

Perfluorooctane sulfonate (PFOS) is found ubiquitously in the environment, and is known to cause developmental toxicity, including cleft plate (CP). The aim of the present study was to elucidate the mechanism of CP associated with in utero exposure to PFOS in mice.It was first examined whether the concentration of PFOS in fetal serum was related to susceptibility to CP. Palatogenesis following the administration of various concentrations of PFOS to dams was compared. A histological examination was conducted on gestational day (GD) 15 and 18, and alizarin red/alcian blue staining of fetal heads on GD18. Finally, cultured palatal shelves (PSs) of GD14 fetuses, which had not yet made contact with each other, for 48 h, were examine whether the shelves maintained the ability to fuse. The incidence of CP increased from 7.3% with a fetal serum concentration of PFOS of 110.7±13.4µg/ml (13 mg/kg) to 78.3% with 138.6±0.9µg/ml (20 mg/kg). PFOS at 50 mg/kg on GD11–15 caused CP at a rate of 6.1%, meanwhile PFOS at 20 mg/kg on GD1–17 caused a CP rate of 89.3%. Failure of palatal shelf elevation was observed with 20 mg/kg PFOS. PFOS at 20 mg/kg on GD1–17 and 50 mg/kg on GD11–15 inhibited mandibular growth to the same extent, even though the rate of CP was different. Explants exposed to PFOS 20 mg/kg and Tween 20 showed 94% (34/36) and 100% (31/31) fusion, respectively. It was demonstrated that increasing the oral dose of PFOS from 13 to 20 mg/kg resulted in a significant increase in CP even though there was only a small increase in serum concentration of PFOS. PFOS prevented elevation of the PSs above the tongue because their growth/fusion potentialwas maintained. Mandibular hypoplasia did not seem to play a critical role in the pathogenesis of CP.