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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
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other: GLP compliant study, available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Objective of study:
excretion
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The objectives of the study were to evaluate the pharmacokinetic (in blood) and excretion profiles of the test article in rats. Difluoro [1,1,2,2-tetrafluoro-2-(pentafluoro-ethoxy)] ethoxy acetic acid (EEA) in the vehicle, sterile water for injection, was administered intravenously once to 1 pharmacokintic (blood collection) group and 1 excretion group of Crl:CD(SD) rats.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Difluoro [1,1,2,2-tetrafluoro-2-(pentafluoro-ethoxy)] ethoxy acetic acid (EEA)
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
intravenous
Vehicle:
water
Duration and frequency of treatment / exposure:
once
Doses / concentrations
Remarks:
Doses / Concentrations:
10 mg/kg bw at a dosage volume of 5 mL/kg
No. of animals per sex per dose:
The pharmacokinetic group consisted of 9 animals/sex and the excretion group consisted of 3 animals/sex
Control animals:
no
Positive control:
none
Details on dosing and sampling:
All animals were observed twice daily for mortality and moribundity. Detailed physical examinations were performed at least once during the pre-treatment period. Individual body weights were recorded during acclimation, at pretest initiation, at randomization and on study day 0. Food consumption was recorded during the pretest period only.
For pharmacokinetic assessment, blood samples were collected on wet ice from 3 animals/sex prior to dosing and at approximately 2, 10, 20 and 30 minutes and 1, 3, 5, 7, 24 and 48 hours after dose administration.
For excretion profile, urine samples were collected from 3 animals/sex over the following intervals: 0-6, 6-12 and 12-24 hours post-dosing.
All pharmacokinetic and excretion group animals were euthanized and discarded without further evaluation following the final blood or urine collection.
Serum and urine concentrations of EEA were measured using a validated LCMS/MS method. The concentrations in serum and amounts excreted in urine were used for pharmacokinetic analysis.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
After a single intravenous dose of EEA at 10 mg/kg bw, systemic exposure (AUC0-∞) to EEA for male rats was almost 7-fold higher than for female rats. EEA appeared to remain mostly in the circulation in male rats (apparent volume of distribution about 0.2 L/kg), but to have extensive tissue distribution in female rats (apparent volume of distribution of more than 2.5 L/kg).
Details on excretion:
The terminal elimination phase for EEA in serum had a half-life of 9.4 and 5.4 hours for female and male rats, respectively. The half-life for EEA in urine was 1.8 and 3.2 hours, for female and male rats respectively. Nevertheless, the percent of EEA dose eliminated over 24 hours post-dosing in the urine of male rats and female rats was similar (approximately 65%). This can be explained by the lower amounts of EEA available for urinary clearance in the circulation of female rats compared to male rats as suggested by the differences in the apparent volume of distribution.

Metabolite characterisation studies

Metabolites identified:
not measured

Applicant's summary and conclusion