Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically acceptable method, study performed prior to introduction of GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1972
Report date:
1972

Materials and methods

Objective of study:
metabolism
Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 417 (Toxicokinetics)
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
EC Number:
248-421-0
EC Name:
Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
Cas Number:
27344-41-8
Molecular formula:
C28H22O6S2.2Na
IUPAC Name:
disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
Details on test material:
- Specific activity (if radiolabelling): 2.09 µCi per mg
- Locations of the label (if radiolabelling): beta position of the ethylene bridge
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
SIV 50
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ivanovas, Kisslegg, Germany
- Weight at study initiation: approximately 200 g
- Individual metabolism cages: yes

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: C14-test substance was dissolved in water and approximately 0.5 ml of solution was adininistered by stomach tube. The dose received by the rats was 5.53 ± 0.03 mg/kg , (mean ± SD),
Duration and frequency of treatment / exposure:
one single administration
Doses / concentrations
Remarks:
Doses / Concentrations:
5000 mg/kg
No. of animals per sex per dose / concentration:
4
Control animals:
no
Positive control reference chemical:
no
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, expired CO2, blood, liver, kidney, brain, muscel, fat, cage wash
- Time and frequency of sampling: 96 hours after admininistration; Faeces, urine and expired CO2 were collected separately at predetermined time intervals for analysis.


METABOLITE CHARACTERISATION STUDIES
- Tissues and body fluids sampled: faeces
- Time and frequency of sampling: no data
- From how many animals: 4 (samples pooled)
- Method type(s) for identification: TLC

Results and discussion

Main ADME resultsopen allclose all
Type:
excretion
Results:
More than 90 per cent of the administered radioactivity was excreted within 48 hours of dosing. The faeces being the main, and practically only, route of elimination. Little or no radioactivity was found in the urine and expired air.
Type:
distribution
Results:
Blood, muscle, fat, brain, kidney and liver were examined for residual radioactivity. Residues in all tissues were less than 0.01 ppm.
Type:
metabolism
Results:
not metabolised in rat after oral administration

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
Practically all the radioactivity in the faeces was extractable with methanol; (94 % for males and 96 % for females). Thin layer chromatography of the extract showed that the extracted radioactivity from both sexes co-chromatographed exactly with the UV-treated parent compound. The thin layer chromatography results suggest that test substance is converted from the trans-trans isomer to the cis-trans or cis-cis during its passage through the gut.

Any other information on results incl. tables

Excretion of Radioactivity:

 

Excretion

 

male

female

Faeces: 0 - 24 h

86.8 ± 6.9

72.7 ± 15.9

            24 – 48 h

6.6 ± 4.1

22.4 ± 15.2

            48 – 72 h

0.9 ± 0.8

0.4 ± 0.3

            72 – 96 h

0.5 ± 0.5

0.5 ± 0.3

Total

94.8 ± 3.2

96.0 ± 1.0

Urine: 0 - 96 h

0.03 ± 0.01

0.03 ± 0.01

Expired Air: 0 – 48 h

< 0.01

< 0.01

Cage

0.09 ± 0.1

0.03 ± 0.03

Total Recovery

94.9 ± 3.2

96.2 ± 1.0

Excretion Half-Life Time

8.2 h

13.6 h

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
The above results indicate that test substance is neither absorbed nor metabolised in the rat. The rate of excretion is probably only dependent on the rate at which it passes through the gastro-intestinal tract.