Hexasodium 2,2'-[vinylenebis[(3-sulphonato-4,1-phenylene)imino[6-[bis(2-hydroxyethyl)amino]-1,3,5-triazine-4,2-diyl]imino]]bis(benzene-1,4-disulphonate)

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

other: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Test procedures cannot be subsumed under a testing guideline, nevertheless are well documented and scientifically acceptable

Remarks:

.

Justification for type of information:

Justification for Read Across is attached in Section 13 of this dossier

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Reference 2

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

Principles of method if other than guideline:

The fate of 14C-labeled test substance (TS) was followed in the rat. An oral dose of approximately 5 mg/kg was administered to animals. Faeces, urine and expired CO2 were collected separately at predetermined time intervals for analysis. The animals were killed by decapitation 96 hours after dosing.

GLP compliance:

no

Remarks:

Pre GLP.

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 4,4'-bis[[6-anilino-4-[(2-hydroxyethyl)methylamino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate

EC Number:

237-600-9

EC Name:

Disodium 4,4'-bis[[6-anilino-4-[(2-hydroxyethyl)methylamino]-1,3,5-triazin-2-yl]amino]stilbene-2,2'-disulphonate

Cas Number:

13863-31-5

Molecular formula:

C38H40N12Na2O8S2

IUPAC Name:

disodium 2,2'-ethene-1,2-diylbis[5-({4-anilino-6-[(2-hydroxyethyl)(methyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate]

Radiolabelling:

yes

Remarks:

C14

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: average was 229 ± 14 g.
- Housing: kept separately.
- Individual metabolism cages: yes, all-glass metabolism cages.
- Diet: commercial rat food (Nafag No. 185, Nafag, Gossau, Switzerland).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS
Test substance was dissolved in water and approx. 0.5 ml of solution was administered.

Duration and frequency of treatment / exposure:

Once.

Doses / concentrations

Remarks:

Doses / Concentrations:
5.23 ± 0.05 mg/kg

No. of animals per sex per dose / concentration:

4 males and 4 females.

Details on study design:

The animals were killed by decapitation 96 hours after dosing.

Details on dosing and sampling:

PHARMACOKINETIC STUDY
- Sampling in life: faeces, urine and expired CO2 were collected separately at predetermined time intervals for analysis.
- Tissues sampled: samples of blood, liver, kidney, brain, muscle and fat were collected for analysis.
- Time and frequency of sampling: tissues and blood after 96 hours.

Statistics:

Excretion half-life times were calculated from the net rate coefficient of drug elimination using the 24-hour excretion values.
The limit of quantitative determination was calculated according to C.A. carrie (Ami. Chem. 40, 596, (1968) ).

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The results indicate 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 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 supprising as this compound is known to bind very tightly to cellulose and is probably bound to the same substance in the rat faeces.

Any other information on results incl. tables

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.

Executive summary:

Method

The fate of 14C-labeled test substance (TS) was followed in the rat. An oral dose of approximately 5 mg/kg was administered to animals. Faeces, urine and expired CO2 were collected separately at predetermined time intervals for analysis. The animals were killed by decapitation 96 hours after dosing.

Result

After dosing nearly all the administered radioactivity was rapidly excreted with the faeces.

The average residue in all tissues examined was less than 0.005 ppm TS equivalents. Most of the radioactivity in the faeces was not extractable with either methanol or water. Probably because the compound is tightly bound to cellulose in the faeces.