1,1,2,2,3,3,4,4,4-nonafluoro-N-(2-hydroxyethyl)-N-methylbutane-1-sulphonamide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 April 2002 to 10 May 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study was performed using a defined internal protocol, but not performed under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

according to guideline

Guideline:

other: Protocol number ST-75

GLP compliance:

no

Remarks:

Study was not performd under GLP conditions, but met the internal Strategic Toxicology Laboratory GLP program procedure.

Test material

Test material information

Constituent 1

Reference substance name:

T-7599

IUPAC Name:

T-7599

Details on test material:

- Name of test material (as cited in study report):N-Methyl perfluorobutylsulfonamido ethyl alcohol; N-MeFBSE alcohol or C4 alcohol, T-7599
- Physical state: Solid
- Lot/batch no.: Lot 6
- Storage condition of test material: Stored tightly sealed at room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan
- Age at study initiation: 6-8 weeks in age
- Weight at study initiation: approx. 150-250 grams
IN-LIFE DATES: From: 29 April 2002 To: 10 May 2002

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Duration and frequency of treatment / exposure:

Treatment time was temporary during the single dose oral gavage time.

Doses / concentrations

Remarks:

Doses / Concentrations:
30 mg/kg dose of the test compound in propylene glycol at a volume of 5 mL/kg.

No. of animals per sex per dose / concentration:

N=3/dose group/exposure period.

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 4 days (100 hours)
- Frequency of observations and weighing: at 4 hours, 28 hours and 100 hours
- Necropsy of survivors performed: Yes
- Other examinations performed:body and liver weights, gross necropsy

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled (delete / add / specify); serum and liver. Urine was stored and collected for future analysis.
- Time and frequency of sampling: at 4 hours, 28 hours and 100 hours
METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled (delete / add / specify):serum and liver
- Time and frequency of sampling: at 4 hours, 28 hours and 100 hours
- From how many animals: (samples pooled or not): 42 total, seven of which were treated with the test article, 6 controls , the remainder were animals tested with other similar compounds.
- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC): GC, GC/MS, LC/MS, 1H-NMR and 19F-NMR techniques. 15 samples of liver from the entire study were submitted for total fluorine analysis using 9000F Flouride Analysis System.
- Limits of detection and quantification: The LOD of the total fluorine analytical method used was 0.5 ppm and each sample was analyzed in triplicate.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

5.2% absorption in both serum and in the liver, 28 hours post dose.

Toxicokinetic parameters

Toxicokinetic parameters:

other: Apparent serum half-life was approximately 17 hours.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Fluorine concentrations were measured.

Any other information on results incl. tables

There were no significant effects of treatment on body weights or liver weights. All animals gained weight over the course of the study period. Gross necropsy observations showed that all organ tissues appeared to be normal when compared to the controls, except that mottled kidneys were found for some animals that received treatments. The kidney mottling was most likely due to blood pooling in the kidneys at necropsy and was not considered to be compound-related. Animals that received the test article at 30 mg/kg had average total fluorine concentrations in serum of 10.8 ppm on day zero (4 hours post dose), 23.1 ppm on day one (28 hours post dose) and 1.0 ppm on day four (100 hours after dose). The half life elimination times for the test compound in the serum was 17 hours. The average liver total fluorine concentrations were 14.1, 18.3 and 2.2 ppm after 4 hours, 28 hours or 100 hours post dose, respectively. The apparent total fluorine elimination rates were similar in both serum and liver for animals treated with the test compound.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): other: Limitations do not allow concl. on the time post-dose at which the max. tissue total organic fluorine conc. were achieved, or possible multiphasic elimin. patterns. The subsance would not be exp. to significantly accumul. in liver/serum upon repeat. exp.
The test compound elimination half life is significantly less than 4 days in both the serum and liver of rats (of approximately 17 hours). The test compound would not be expected to significantly accumulate in the liver or serum following repeated exposure.

Executive summary:

Male Sprague-Dawley rats received a single 30 mg/kg dose of the test compound in propylene glycol by oral gavage at a volume of 5 mL/kg body weight. The vehicle control group rats received a single dose of ethylene glycol at a volume of 5 mL/kg. Necropsies were performed at 4 hours, 28 hours and 100 hours post dose. At necropsy there were no significant differences in body weight or gross macroscopic observations between any of the treatment groups and the control group. The apparent elimination half-life of three compounds were compared to the half-life of PFBS in liver and serum. The apparent serum half-life for the percentage for the test compound dose absorbed and present in the serum and liver were estimated as 5.2%, both in the serum and in the liver 28 hours post dose.