Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-03-26 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 guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1992
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987-02-24
GLP compliance:
yes (incl. certificate)
Remarks:
signed 1996-02-27
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: approximately ten to fourteen weeks old
- Weight at study initiation: males: 210 to 218 g; femlaes: 200 to 204 g
- Housing: the animals were housed in suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (ad libitum): Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK
- Water (ad libitum): mains drinking water
- Acclimation period: minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 22°C
- Relative humidity: 48 to 53%
- Air exchanges: approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the test material was used as supplied. The specific gravity (specific gravity: 1.065) was determined and used to calculate the appropriate dose volume for the required dose level.

TEST SITE
- Area of exposure: on the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers. The calculated volume of the test material (dose volume: 18.78 mL/kg) was applied uniformly to an area of shorn skin (approximating to 10% of the total body surface area) using a graduated syringe.

- Type of wrap if used: a piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The bandage was further secured with a piece of BLENDERM wrapped around each end. The animals were caged individually for the exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: after the 24-hour contact period
- Washing: the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animas were returned to group housing for the remainder of the study period.





Duration of exposure:
24 hours
Doses:
20000 mg/kg (2000 mg/kg active ingredient)
No. of animals per sex per dose:
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.
After removal of the dressing and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scroed according to the Draize scale. Any other skin reactions, if present were also recorded.
Individual bodyweights were recorded prior to application of the test material 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. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 10% aqueous solution of the test material HR 96/N00002
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed expected gain in bodyweight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
- Other observations: no signs of skin irritation were noted during the study.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 20000 mg/kg bodyweight (2000 mg/kg active ingredient).
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not classified as acute toxic via the dermal route.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as acute toxic via the dermal route.