Tetraethylammonium heptadecafluorooctanesulphonate

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

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:

Gene expression profiling in the liver and lung of perfluorooctane sulfonate-exposed mouse fetuses: Comparison to changes induced by exposure to perfluorooctanoic acid

Author:

Rosen MB, Schmid JE, Das KP, Wood CR, Zehr RD, Lau C

Year:

2009

Bibliographic source:

Reprod toxicol 27, 278-288

Materials and methods

Type of study / information:

Gene expression in the liver and lung of perfluorooctane sulfonate-exposed mouse fetuses

Principles of method if other than guideline:

Pregnant CD-1 micewere dosed with 0, 5, or 10 mg/kg PFOS fromgestation days 1–17. Transcript profiling was conducted on the fetal liver and lung.

GLP compliance:

no

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, Sigma Aldrich, St. Louis, MO)

Results and discussion

Any other information on results incl. tables

Exposure to PFOS had no observable effect on the body weight or general appearance of the dams utilized in the study, nor was

litter size affected by PFOS treatment (data not shown). Hematoxylin and eosin stained sections from representative treated

and control fetal tissues are shown in Fig. 1. Eosoinphilic granulescharacteristic of peroxisome proliferation were observed in liver sections from both PFOS dose groups, although such changes were not uniformly distributed across all sections as previously

observed in the PFOA-exposed fetal liver. No apparent treatment effectswere observed in the fetal lung by conventional bright

field microscopy.

PFOS up-regulated a number of putative markers of PPAR-alpha activity in the fetal liver, whereas, regulation of a more limited group of genes such as Cyp4a14, enoyl-Coenzyme A hydratase (Ehhadh), and fatty acid binding protein 1 (Fabp1) was observed in the fetal lung. Canonical pathways or functional groups significantly enriched by PFOS included fatty acid metabolism in the fetal liver and lung along with xenobiotic metabolism, peroxisome biogenesis, cholesterol biosynthesis, bile acid biosynthesis, and metabolism of glucose and glycogen.

In summary, most of the transcriptional changes induced by PFOS in the fetal mouse liver and lung were related to activation

of PPAR-alpha. When compared to the transcript profiles induced by PFOA, few remarkable differences were found other than upregulation of Cyp3a genes. These data suggest that changes related to PFOS-induced neonatal toxicity may not be evident in the

fetal transcriptome at term. Therefore, the mode of action of PFOS-induced neonatal toxicity remains uncertain, although by default these data lend support to the hypothesis that variables related to the physical properties of the chemical, such as altered fluid dynamics of pulmonary surfactant, may be associated with a PPAR-alpha-independent mode of action in PFOS-exposed rodent

neonates.

Applicant's summary and conclusion

Executive summary:

Pregnant CD-1 micewere dosed with 0, 5, or 10 mg/kg PFOS fromgestation days 1–17. Transcript profiling was conducted on the fetal liver and lung.

PFOS-dependent changes were primarily related to activation of PPAR-alpha. No remarkable differences were found between PFOS and PFOA. Given that PPAR-alpha signaling is required for neonatal mortality in PFOA-treated mice but not those exposed to PFOS, the neonatal mortality observed for PFOS may reflect functional deficits related to the physical properties of the chemical rather than to transcript alterations.