Disodium [(9,10-dihydro-9,10-dioxo-1,4-anthrylene)bis[imino(3-methylpropane-1,3-diyl)]]bis(benzenesulphonate)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08 September 2015 to 23 September 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

- see below

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

- see below

Principles of method if other than guideline:

The temperature was out of the target range during the acclimation period, (maximum of 26.3 °C). The relative humidity was out of the target range during the experiment, (minimum of 24 %).
These deviations have no presumed effect on the outcome or validity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Disodium [(9,10-dihydro-9,10-dioxo-1,4-anthrylene)bis[imino(3-methylpropane-1,3-diyl)]]bis(benzenesulphonate)

EC Number:

274-999-9

EC Name:

Disodium [(9,10-dihydro-9,10-dioxo-1,4-anthrylene)bis[imino(3-methylpropane-1,3-diyl)]]bis(benzenesulphonate)

Cas Number:

70900-27-5

Molecular formula:

C34H32N2O8S2.2Na

IUPAC Name:

Disodium [(9,10-dihydro-9,10-dioxo-1,4-anthrylene)bis[imino(3-methylpropane-1,3-diyl)]]bis(benzenesulphonate)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Appearance: Blue powder
- Storage conditions of test material: Room temperature 15-25 °C, below 70 RH %, protected from light and humidity

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: CRL:(WI) (SPF)
- Age at study initiation: 9 weeks old
- Weight at study initiation: 183 to 213 g
- Fasting period before study: Overnight food withdrawal prior to dosing. Food was made available again 3 hours after the treatment.
- Housing: 3 animals per cage in Type II polypropylene/polycarbonate cages with wooden chips available as bedding
- Diet: ad libitum
- Water: ad libitum access to tap water from the municipal supply in a 500 mL bottle
- Acclimation period: 12, 13 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20.0 to 26.3 °C
- Relative Humidity: 24 to 68 %
- Air changes: 15 to 20 air exchanges/hour
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES
From: 27 August 2015
To: 22 and 23 September 2015

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The test material was freshly formulated on the day of administration. The formulation container was stirred continuously up to the end of dose administration procedures.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The initial dose level was selected to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 females per dose
Two groups of 3 female rats were treated with the test material at 2000 mg/kg, Group 1 and Group 2

Control animals:

no

Details on study design:

- Dosing: Initially, 3 female animals were treated with 2000 mg/kg bw of test material. No mortality was observed, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
- Necropsy of survivors performed: Yes, macroscopic examination was performed on all animals. The animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthanimal® 40 % injection). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed and macroscopic abnormalities were recorded.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Acute oral administration of test material caused symptoms of liquid faeces and coloured faeces in all animals; the symptoms appeared after 3 hours of dosing in 4 animals and 4 hours after dosing in 2 animals. From Day 2 all animals became symptom-free.

Gross pathology:

No abnormalities were noted at necropsy; there were no macroscopic observations.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study, the LD50 was determined to be >2000 mg/kg bw in female rats.

Executive summary:

The acute oral toxicity of the test material was assessed in accordance with the standardised guidelines OECD 423 and EU Method B.1 tris under GLP conditions.

Two groups of 3 female CRL:(WI) rats were treated with the test material in distilled water at a dose level of 2000 mg/kg bw (Group 1 and Group 2). A single oral treatment was carried out by gavage for each animal at a dose volume of 10 mL/kg bw.

Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore no further testing was required.

Clinical observations were performed, body weight was measured and all animals were subjected to a necropsy and a macroscopic examination. At study termination animals were subjected to a macroscopic examination.

No mortalities were observed. Liquid faeces and coloured faeces were observed in all animals on the day of dosing. The test material had no effect on body weight and no abnormalities were noted at necropsy.

Under the conditions of this study, the LD50 was determined to be >2000 mg/kg bw in female rats.