Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
according to guideline
Guideline:
other: EPA OPPTS 870.3100 (90-Day Oral Toxicity in Rodents)
Deviations:
no
Remarks:
The study was conducted according to guideline in effect at time of study conduct
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctan-1-ol
EC Number:
211-477-1
EC Name:
3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctan-1-ol
Cas Number:
647-42-7
Molecular formula:
C8H5F13O
IUPAC Name:
3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctan-1-ol
Details on test material:
- Purity: 99.7%
Radiolabelling:
no

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% (w/v) aqueous methylcellulose prepared in reverse osmosis deionised water.
Duration and frequency of treatment / exposure:
daily for 90 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 5, 25, 125, and 250 mg/kg/day (males and females)
No. of animals per sex per dose / concentration:
10 rats/sex/dose (main study), 10 rats/sex/dose (1-month recovery), 5 rats/sex/dose (3-month recovery)
Control animals:
yes, concurrent vehicle

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
Liver- or fat-to-plasma ratios did not indicate preferential retention in these organs. Using the plasma concentrations of 5-3A as a marker for internal exposure shows that female rats have a higher internal dose than the male rats. Male rats reached saturation at the 125 mg/kg/day dose level.
Details on excretion:
It is likely that the presence of 5-3A, 4-3A and PFPeA in the 1- and 3-month recovery samples reflects the biphasic elimination common to this class of test materials. This biphasic elimination is characterized by an initially rapid elimination of the majority of the test material followed by a slower elimination of a small fraction.

Metabolite characterisation studies

Metabolites identified:
yes
Details on metabolites:
5-3A (F(CF2)5CH2CH2COOH) was the major metabolite observed in the plasma, liver, and fat samples at all dose levels and in both sexes. The metabolites 4-3A (F(CF2)4CH2CH2COOH) and PFPeA (F(CF2)4COOH) were also observed but in much lower concentrations than 5-3A.

Applicant's summary and conclusion

Conclusions:
5-3A (F(CF2)5CH2CH2COOH) was the major metabolite.
Liver- or fat-to-plasma ratios did not indicate preferential retention in these organs.
Elimination was biphasic (initial rapid elimination of the majority of the test material followed by a slower elimination of a small fraction).
Executive summary:

In a 90-day study, male and female rats were dosed by oral gave at dose levels of 0, 5, 25, 125, and 250 mg/kg/day. At the time of sacrifice on the day following the last administration of the test substance or at the end of the 1-month and 3-month recovery periods, blood (then processed to plasma), liver and fat samples were collected from all rats assigned to the main study and 1 and 3 month recovery periods for analyses of test substance and/or metabolite. The test substance, and proposed metabolites, PFBuA (F(CF2)3COOH), PFPeA (F(CF2)4COOH), PFHxA (F(CF2)5COOH), PFHpA (F(CF2)6COOH), 5-3A (F(CF2)5CH2CH2COOH), 6-2A (F(CF2)6CH2COOH), 6-2UA (F(CF2)5CF=CHCOOH), and 4-3A (F(CF2)4CH2CH2COOH) were quantified by LC/MS/MS analysis. Based on the toxicokinetic evaluation, the plasma, liver and fat samples displayed that 5-3A (F(CF2)5CH2CH2COOH) was the major metabolite observed at all dose levels and in both sexes. The 4-3A (F(CF2)4CH2CH2COOH) and PFPeA (F(CF2)4COOH) metabolites were also observed but in much lower concentrations than 5-3A. Liver- or fat-to-plasma ratios did not indicate preferential retention in these organs. Using the plasma concentrations of 5-3A as a marker for internal exposure shows that female rats have a higher internal dose than the male rats. Male rats reached saturation at the 125 mg/kg/day dose level. It is likely that the presence of 5-3A, 4-3A and PFPeA in the 1- and 3-month recovery samples reflects the biphasic elimination common to this class of test materials. This biphasic elimination is characterized by an initially rapid elimination of the majority of the test material followed by a slower elimination of a small fraction.