Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

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: Basic data given: comparable to guidelines/standards

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973
Reference Type:
publication
Title:
Metabolic Behaviour of Water-Soluble Fluorescent Whitening Agents in the Rat and Bean Plant
Author:
W. Muecke, G. Dupuis, H.O. Esser
Year:
1975
Bibliographic source:
Environmental Quality and Saftety, Supplement, Vol 4, 174-179

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 417 (Toxicokinetics)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Specific activity (if radiolabelling): 10.5 µCi/mg
Radiolabelling:
yes
Remarks:
C14

Test animals

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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: test substance was dissolved in water

Duration and frequency of treatment / exposure:
treatment: once
sample preparation 96 hours later
Doses / concentrations
Remarks:
Doses / Concentrations:
5.23 ± 0.05 mg/kg (mean ± SD)
No. of animals per sex per dose:
4
Control animals:
no
Details on dosing and sampling:
PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled: urine, faeces, expired CO2, blood, liver, kidney, brain, muscle, fat, cage washes
- Time and frequency of sampling: tissues and blood after 96 hours; urine, faeces and expired air see result table 1

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The results indicate (see Details on excretion) that test substance is not absorbed from the gut of the rat and probably passes through the gut tightly bound to cellulose in the gut contents. The rate of excretion is probably only dependent on the rate at which the gut contents pass through the gastro-intestinal tract.
Details on distribution in tissues:
The animals were killed 96 hours after dosing and samples of blood, muscle, fat, brain, liver and kidney examined for residual radioactivity. The average residue in all tissues of both sexes was less, than 0.005 ppm test substance equivalents (limit of quantitative determination).
Details on excretion:
More than 90% 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. The faeces were lyophilized, ground to a fine powder, and exhaustively extracted in a Soxhlet apparatus, first with methanol and second with water. Practically no radioactivity was extracted with these solvents. This is not entirely suprising as this compound is known to bind very tightly to cellulose and is probably bound to the same substance in the rat faeces.

Metabolite characterisation studies

Metabolites identified:
not measured

Any other information on results incl. tables

Table 1: Excretion of Radioactivity by Rats after an oral Dose of approximately 5 mg/kg 14C-test substance:

 

Excretion

 

Males; n = 3*

Females, n = 4

Faeces

 

 

0 - 24 h

74.8 ± 10.6

83.9 ± 9.0

24 - 48 h

18.1 ± 10.5

11.2 ± 7.1

48 - 72 h

0.4 ± 0.2

0.3 ± 0.2

72 - 96 h

0

0.1 ± 0.1

Subtotal

93.3 ± 6.2

95.5 ± 2.8

 

 

 

Urine

 

 

0 - 96 h

93.3 ± 6.2

95.5 ± 2.8

 

 

 

Expired Air

 

 

0 - 72 h

< 0.01

< 0.01

 

 

 

Cage wash

0.04 ± 0.02

0.3 ± 0.2

 

 

 

Total Recovery

93.6 ± 5.6

96.1 ± 2.7

 

 

 

Excretion half-life time (h)

13.8

9.5

*: The result from one male were excluded from table because of a dosing error

Applicant's summary and conclusion

Conclusions:
After an oral dose of approximately 5 mg/kg nearly all the administered radioactivity was rapidly excreted with the faeces.