Disodium 2,2'-[(9,10-dihydro-9,10-dioxo-1,4-anthrylene)diimino]bis[3-bromo-5-butyltoluene-4-sulphonate]

Endpoint summary

Description of key information

Acute toxicity: oral. Driscoll (1993)

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 August 1993 to 21 September 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately five to eight weeks old
- Weight at study initiation: males weighed 144 - 164g, and the females 130 - 150g
- Fasting period before study: overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: The animals were housed in groups of five by sex in solid-floor polypropylene cages with sawdust bedding.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum period of at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 - 22 °C
- Humidity: 49 - 60 %
- Air changes: approximately 15 changes per hour
- Photoperiod: lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

VEHICLE
- For the purpose of the study the test material was freshly prepared, as required, as a suspension at the appropriate concentration in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: A range-finding study was performed to establish a dosing regime as follows: 1 male and 1 female were treated at 2000 mg/kg and the animals were observed for deaths or overt signs of toxicity 1/2,1, 2 and 4 hours after dosing and subsequently once daily for 5
days. Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed. Based on the results of the range-finding study a further group of 5 male and 5 female animals was treated at 2000 mg/kg.

Doses:

All animals were dosed once only by gavage at 2000 mg/kg using a metal cannula attached to a graduated syringe.

No. of animals per sex per dose:

Range-finding study: 1 animalsper sex per dose
Main study: 5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for 5 days (range-finding study) or 14 days (main study).
- Frequency of observations and weighing: Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14 (main study).
- Necropsy of survivors performed: No necropsy was performed on range-finding animals. At the end of the main study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

EVALUATION OF DATA
Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.
The results were interpreted according to the Commission Directive 91/325/EEC which adapts Council Directive 67/548/EEC on the regulations relating to the classification, packaging and labelling of dangerous substances as follows:
Interpretation according to Annex VI Part II (D)
The test material will be classified and assigned the appropriate symbol and risk phrase as follows:
VERY TOXIC: Acute oral LD50 ≤25 mg/kg (T+, R 28 "VERY TOXIC IF SWALLOWED")
TOXIC: Acute oral LD50 >25 to 200 mg/kg (T, R 25 "TOXIC IF SWALLOWED")
HARMFUL: Acute oral LD50 >200 to 2000 mg/kg (Xn R 22 "HARMFUL IF SWALLOWED")
Test materials with acute oral LD50 values greater than 2000 mg/kg require no symbol and risk phrase.

Preliminary study:

- There were no deaths. A dark blue-coloured discharge from the anus was noted two and/or four hours after dosing. Blue-coloured staining of the fur was noted one day after dosing.
- Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: A blue-coloured discharge from the anus was noted in all animals two and/or four hours after dosing. Blue-coloured staining of the fur was commonly noted.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.

Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 401 and EU Method B1, under GLP conditions.

A range-finding study was performed dosing one male and one female at 2000 mg/kg, there were no deaths observed. A dark blue-coloured discharge from the anus was noted two and/or four hours after dosing. Blue-coloured staining of the fur was noted one day after dosing. Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.

For the main study five male and five female rats were dosed once by oral gavage at 2000 mg/kg. There were no deaths and all animals showed expected gain in bodyweight during the study. A blue-coloured discharge from the anus was noted in all animals two and/or four hours after dosing. Blue-coloured staining of the fur was commonly noted. No abnormalities were noted at necropsy.

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity: oral. Driscoll (1993)

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 401 and EU Method B1, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

A range-finding study was performed dosing one male and one female at 2000 mg/kg, there were no deaths observed. A dark blue-coloured discharge from the anus was noted two and/or four hours after dosing. Blue-coloured staining of the fur was noted one day after dosing. Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.

For the main study five male and five female rats were dosed once by oral gavage at 2000 mg/kg. There were no deaths and all animals showed expected gain in bodyweight during the study. A blue-coloured discharge from the anus was noted in all animals two and/or four hours after dosing. Blue-coloured staining of the fur was commonly noted. No abnormalities were noted at necropsy.

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute oral toxicity.