Reaction mass of tetrasodium 8,8'-(1E,1'E)-(4,4'-(cyclohexane-1,1-diyl)bis(4,1-phenylene))bis(diazene-2,1-diyl)bis(7-hydroxynaphthalene-1,3-disulfonate) and trisodium 7-hydroxy-8-((E)-(4-(1-(4-((E)-(1-hydroxy-4-sulfonatonaphthalen-2-yl)diazenyl)phenyl)cyclohexyl)phenyl)diazenyl)naphthalene-1,3-disulfonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Remarks:

constituent 1

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

The complete Read Across Approach is attached at section 13. Source study has reliability 1.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1973

Report date:

1973

Materials and methods

Principles of method if other than guideline:

In order to determine the dose/response relationship of the test substance, groups of 5 male and 5 female rats were dosed with various single doses (i.e. 1000, 3000, 6000, 10000 and 15000 mg/kg) of the compound, diluted in distilled water by gavage. Symptoms and mortality after administration were recorded during an observation period of 15 days. The LD50 was calculated by probit analysis method.

GLP compliance:

no

Remarks:

pre GLP

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Similar Substance 01

IUPAC Name:

Similar Substance 01

Test animals

Species:

rat

Strain:

other: Tif RAI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young, unspecified.
- Weight at study initiation: 100 g.
- Housing: animals were housed in groups of 5 in macrolon cages (Size 3).
- Fasting period before study: fasted overnight.
- Diet: standard diet of Nafag, ad libitum.
- Water: drink water, ad libitum.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 1 °C
- Relative humidity: 55 ± 5 %
- Photoperiod: 12 hours cycle dark/light.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Doses:

1000, 3000, 6000, 10000 and 15000 mg/kg

No. of animals per sex per dose:

5 × sex × doses

Details on study design:

- Duration of observation period following administration: 15 days.
- Frequency of observations and weighing: symptoms and mortality were monitored but the frequency was not specified.

Statistics:

The LD50 was calculated by probit analysis method (maximum likelyhood, Goulden A., Methods of Statistical Analysis, John Wiley and Sons, 1960, 3rd printing, pages 404-408).

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 955 mg/kg bw

Based on:

test mat.

95% CL:

3 960 - 6 200

Effect levels 2

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 459.5 mg/kg bw

Based on:

act. ingr.

Mortality:

One female died at 1000 mg/kg after two days from the tretment.
At 6000 mg/kg 3 males and 3 females died.
At the doses of 10000 and 15000 mg/kg all animals died after 1 day from the substance administration.

Clinical signs:

Reduction in spontaneous motility, slight ataxia, diarrhea, ditto and hypoventilation were recorded.

Any other information on results incl. tables

Dose mg/kg	Vehicle	Concentration (%)	Mortality				Bodyweight (g)		Symptoms
			Absolute		%	Day of test	Pre-test	On day 15^th
			M	F
1000	Distilled water	10	0/5	0/5	0	-	100	206	none
3000	Distilled water	10	0/5	1/5	10	2	100	185	transient reduction in spontaneous motility
6000	Distilled water	10	3/5	3/5	60	2-4	100	228	reduction in spontaneous motility, slight ataxia, diarrhea,
10000	Distilled water	10	5/5	5/5	100	1	100	-	ditto, hypoventilation
15000	Distilled water	10	5/5	5/5	100	1	100	-	ditto

Applicant's summary and conclusion

Interpretation of results:

other: not classified, according to the CLP Regulation (EC 1272/2008)

Conclusions:

LD50 is 4955 mg/kg, equivalent to 4459.5 mg/kg as a.i.

Executive summary:

Method

The substance was tested for acute toxicity by oral route. Rats of both sexes were tested at concentration of 1000, 3000, 6000, 10000, 15000 mg/kg, by oral intubation. Physical condition and rate of death were monitored throughout the whole observation period.

Results

The symptoms during the 15 days of observation period were: reduction in spontaneous motility, slight ataxia, diarrhea, ditto, hypoventilation. The acute oral LD50 in rats was calculated to be 4955 mg/kg, equivalent to 4459.5 a.i.. Thus, the compound shows practically no acute toxicity to the rat by this route of administration.