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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Test procedures cannot be subsumed under a testing guideline, nevertheless are well documented and scientifically acceptable. Justification for Read Across is detailed in the Toxicokinetics summary and in the Category Justification Report attached in section 13

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973
Reference Type:
publication
Title:
Unnamed
Year:
1975

Materials and methods

Objective of study:
metabolism
Principles of method if other than guideline:
The behaviour of three water-soluble fluorescent whitening agents (FWAs - including the test item) was studied in rats using 14C-labelled compounds. The fate of 14C-labeled test substance was followed in the rat. The animals dosed with 5.97 ± 0.33 mg/kg (actual dose) and faeces, urine and expired CO2 were monitored. After 96 hours animals were killed and tissues analyzed.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
other: SIV 50
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ivanovas, Kisslegg, Germany
- Breeding: under SPF conditions
- Weight at study initiation: approximately 200 g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Duration and frequency of treatment / exposure:
Single application.
Doses / concentrations
Remarks:
Doses / Concentrations:
6.1 ± 0.1 mg/kg for females and 5.9 ± 0.2 mg/kg for males (mean ± SEM)
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
ANIMALS CONDITION after dosing
- Housing: the animals were kept in all-glass metabolism cages
- Food: ad libitum, commericial food
- Water: ad libitum
- Sacrifice: the animals were killed after 96 hours by decapitation
Details on dosing and sampling:
SAMPLES collaction
- Samples before sacrifice: urine, faeces and expired CO2
- Time and frequency of sampling: 16 or 24, 40 or 48, 64 or 72 hours after application
- Samples after sacrifice: blood, liver, kidney, brain, muscle and fat

ANALYSIS
- Method type for identification: liquid scintillation counting (Model 3375 Tricarb)
- Limits of detection and quantification: 0.01 ppm
- Radioactivity: the radioactivity in the dry material was determined by combustion
- Faeces: TLC (Thin Layer Chromatography)
- Sample preparation: liqui samples were measured directly. Faeces were lyophilized and ground to a fine powder in a disc mill. CO2: expired CO2 was trapped in ethanolamine solution.
- Tissues: animal tissues and blood were solubilized with a 1:1 mixture of 2-propanol:toluene and the resulting solutions were decolorized with hydrogen peroxide before adding the scintillation cocktail for counting.

Results and discussion

Main ADME results
Type:
excretion
Results:
More than 90 % of the administered radioactive material was excreted within 48 hours.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
The results indicate that there is virtually no absorption from the gut of the test substance.
Details on distribution in tissues:
Residues in all tissues investigated were below the limit of quantitative determination which was 0.005-0.01 ppm test item equivalent.
Details on excretion:
The faeces proved to be practically the only route of elimination for the applied radioactive material. About 90 % of the applied radioactivity was eliminated in faeces within 24 hours of dosing, indicating, in combination with the short half life times, that no significant amounts of test substance were absorbed from the gastro-intestinal tract.
Radioactivity found in urine was at the limit of detection (0.02 %. of applied dose).
No radioactivity was found in the expired air (< 0.01 %).
No sex differences were observed.
A calculation of the excretion half life using the net rate coefficient of drug elimination (24 hours excretion value) revealed that 50% of the dose had been excreted within 7-13 hours after dosing.

Metabolite characterisation studies

Metabolites identified:
not measured
Details on metabolites:
The results indicate that there is the test substance is not metabolized by the rats.

Any other information on results incl. tables

The radioactive material present in the faeces of the rats treated with the test substance was not extractable with methanol

Excretion of radioactivity by rats after oral dose

Excretion as a percentage of dose (mean± SEM, n= 4)
Male  Female

Faeces

0-24 hours 76.4 89.6
24-48 hours 20.7 5.6
48-96 hours 0.4 < 0.1
Subtotal 97.5 95.2

Urine  

0-96 hours < 0.1 < 0.1

Expired CO2

0-48 hours < 0.01 < 0.01

Cage wash

< 0.1 < 0.1

Total recovery

97.5 ± 1.8 95.2 ± 1

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
The faeces proved to be practically the only route of elimination (half life ranging from 7-13 hours).
Executive summary:

Method

The behaviour of three water-soluble fluorescent whitening agents (FWAs - including the test item) was studied in rats using 14C-labelled compounds. The fate of 14C-labeled test substance was followed in the rat. The animals dosed with 5.97 ± 0.33 mg/kg (actual dose) and faeces, urine and expired CO2 were monitored. After 96 hours animals were killed and tissues analyzed.

Results

Following oral doses of 5 mg/kg to rats rapid and complete excretion of radioactive material was observed with an excretion half life ranging from 7-13 hours. Faeces were practically the only route of excretion indicating, in combination with the short half life times, that no significant amounts of whitener were absorbed from the digestive tract. No radioactive residues were found in blood, liver, kidney, brain, muscle, or fat 96 hours after dosing (limit of quantitative determination 0.005-0.01 ppm FWA equivalents).