1H-Benzimidazole-5,7-disulfonic acid, 2,2'-(1,4-phenylene)bis-, sodium salt (1:2)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-03-19 to 1996-04-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study reliable without restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1992)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987-02-24

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1996-02-27

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-750-0

EC Name:

-

Cas Number:

180898-37-7

Molecular formula:

C20H12N4O12S4.2Na

IUPAC Name:

disodium dihydrogen 2-[4-(5,7-disulfonato-1H-1,3-benzodiazol-2-yl)phenyl]-1H-1,3-benzodiazole-5,7-disulfonate

Details on test material:

- CAS name: 1H-Benzimidazole-4,6-disulfonic acid-2,2´-(1,4-diphenylene) bis, disodium salt
- Molecular formula: C20H12N4O12S4Na2
- Molecular weight: 674g/mol
- physical state: solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: five to eight weeks of age
- Weight at study initiation: males: 147 to 158 g; females: 132 to 149 g
- Fasting period before study: overnight fast immediately before dosing and for approximately two hours after dosing
- Housing: the animals were housed in groups of up to five by sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet (ad libitum; for exception see "Fasting period before study" above): Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 21°C
- Relative humidity: 39 to 65%
- Air exchanges: approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

RANGE-FINDING STUDY: A range-finding study was performed to establish a dosing regime as follows:
- dose level 2000 mg/kg
- concentration: 200 mg/mL
- dose volume: 10 mL/kg
- number of rats: 1 male / 1 female

The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for five days.
Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.

Results:
There were no deaths or clinical signs of toxicity.
Based on this information, a dose level of 2000 mg/kg bodyweight was selected for the main study.

MAXIMUM DOSE VOLUME APPLIED: the volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
- Dose volume: 10 mL/kg
- Concentration: 200 mg/mL

DOSAGE PREPARATION: the test material was freshly prepared as a suspension at the appropriate concentration in distilled water.

Doses:

2000 mg/kg

No. of animals per sex per dose:

Range-finding study: 1 male / 1 female
Main study: 5 males / 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes; at the end of the 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 for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Results and discussion

Effect levels

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: Hunched posture was noted in one male two and four hours after dosing. No other signs of systemic toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not classified as acute toxic via the oral route.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the oral route.