Tetrasodium 4,4'-bis[[4-[bis(2-hydroxypropyl)amino]-6-[(4-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-stilbene-2,2'-disulphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From April 9 to May 6, 1986.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to internationally accepted testing guidelines and performed according to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetrasodium 4,4'-bis[[4-[bis(2-hydroxypropyl)amino]-6-[(4-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-stilbene-2,2'-disulphonate

EC Number:

267-097-1

EC Name:

Tetrasodium 4,4'-bis[[4-[bis(2-hydroxypropyl)amino]-6-[(4-sulphonatophenyl)amino]-1,3,5-triazin-2-yl]amino]-stilbene-2,2'-disulphonate

Cas Number:

67786-25-8

Molecular formula:

C44H48N12Na4O16S4

IUPAC Name:

tetrasodium 2,2'-ethene-1,2-diylbis[5-({4-[bis(2-hydroxypropyl)amino]-6-[(4-sulfonatophenyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonate]

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna (U.K.) Limited, Wyton, Huntingdon.
- Age at study initiation: approx. five to eight weeks old.
- Weight at study initiation: males 115 - 146 g; females 128 - 140 g.
- Fasting period before study: overnight immediately before dosing and and for approximately two hours after dosing.
- Housing: animals were housed in groups of up to five by sex in polypropylene cages with sawdust bedding.
- Diet: ad libitum, Rat and Mouse Expanded Diet No. 1 (Special Diet Services Limited, Hitham, Essex, U.K).
- Water: ad libitum, drinking water.
- Acclimation period: minimum five days.

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 22 °C
- Humidity: 45 - 60 %
- Air changes: approx. 15 changes per hour.
- Photoperiod: 12 hours light and 12 hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Doses:

5000 mg/kg bw (conc: 250 mg/ml).

No. of animals per sex per dose:

Eleven male and eleven female: two males and two females per dose per group in the range-finding study; 5 males and 5 females in the main study.

Details on study design:

RANGE FINDING
A preliminary study was performed using pre-selected dose levels to determine the highest of these dose levels that produced less than 50 % mortalities as follows: 200, 2000 and 5000 mg/kg bw corresponding to the concentrations of 10.0, 100.0 and 250.0 mg/kg, respectively.
Two males and two females per dose per group were used.

MAIN STUDY
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 1 and 4 hours after dosing and subsequently once daily for 14 days. Mortalities and evidence of overt toxicity were recorded at each observation. Individual bodyweights were recorded on the day of dosing (day 0) and on days 7 and 14.
- Necropsy of survivors performed: yes; all animals were subjected to gross necropsy and examination for any macroscopic abnormalities.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: All treated animals showed hunched posture, pilo-erection and decreased respiratory rate one hour after treatment. Hunched posture and pilo-erection were apparent in all animals at the four-hour observation and on day one. Diarrhoea was noted in several

Gross pathology:

No abnormalities were seen at necropsy on day 14.

Any other information on results incl. tables

RANGE-FINDING STUDY

Dose level (mg/kg)	Sex	Deaths at day						Total deaths
		0	1	2	3	4	5
200	Male	0	0	0	0	0	0	0/4
	Female	0	0	0	0	0	0
2000	Male	0	0	0	0	0	0	0/4
	Female	0	0	0	0	0	0
5000	Male	0	0	0	0	0	0	0/4
	Female	0	0	0	0	0	0

MAIN TEST

Dose level (mg/kg)	Sex	Deaths at day									Total deaths
		0	1	2	3	4	5	6	7	8 - 14
5000	Male	0	0	0	0	0	0	0	0	0	0/10
	Female	0	0	0	0	0	0	0	0	0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information according to the CLP Regulation Criteria used for interpretation of results: EU

Conclusions:

LD50 > 5000 mg/kg bw.

Executive summary:

Method

The acute oral toxicity of the test compound in rats of both sexes was tested at the single concentration of 5000 mg/kg bw and observed over a period of 14 days.

Results

The LD50 is greater than 5000 mg/kg bw.