Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996
Reliability:
1 (reliable without restriction)

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
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris(2-hydroxyethyl)ammonium 7-{4-[4-(2-cyanoamino-4-hydroxy-6-oxidopyrimidin-5-ylazo)benzamido]-2-ethoxy-phenylazo}naphthalene-1,3-disulfonate
EC Number:
421-440-3
EC Name:
Tris(2-hydroxyethyl)ammonium 7-{4-[4-(2-cyanoamino-4-hydroxy-6-oxidopyrimidin-5-ylazo)benzamido]-2-ethoxy-phenylazo}naphthalene-1,3-disulfonate
Cas Number:
778583-04-3
Molecular formula:
Hill formula: C47 H66 N12 O19 S2 CAS formula: C29 H21 N9 O10 S2 x 3 C6 H15 NO3
IUPAC Name:
tris(tris(2-hydroxyethyl)azanium) 2-(cyanoamino)-5-{2-[4-({4-[2-(6,8-disulfonaphthalen-2-yl)diazen-1-yl]-2-methoxyphenyl}carbamoyl)phenyl]diazen-1-yl}-6-hydroxypyrimidin-4-olate

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. Karl Thomae GmbH, Birkendorferstrasse 65, D - 88397 Biberach / Riss, Germany
- Age at study initiation: 15-17 weeks
- Weight at study initiation: 2.8-3.1 kg
- Housing: Individually in stainless steel cages with an automatic cleaning system
- Diet (e.g. ad libitum): Pelleted standard Kliba 341 rabbit maintenance diet ad libitum
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum.
- Acclimation period: Four days under test conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1996-08-07 To: 1996-08-15

Test system

Type of coverage:
semiocclusive
Preparation of test site:
abraded
Vehicle:
water
Controls:
not required
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 h
Observation period:
72h
Number of animals:
1 male, 2 female animals
Details on study design:
TEST SITE
- Area of exposure: back
- coverage: approx. 6 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): skin was flushed with lukewarm tap water
- Time after start of exposure: 4h

SCORING SYSTEM:

ERYTHEMA AND ESCHAR FORMATION
No erythema 0
Very slight erythema (barely perceptible) 1
Well defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4
Maximum possible score 4

EDEMA FORMATION
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well defined by definite raising) 2
Moderate edema (raised approximately 1 mm) 3
Severe edema (raised more than 1 mm and extending beyond area of exposure) 4
Maximum possible score 4

Maximum cumulative score: 8

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 1h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 48h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 72h
Score:
0
Max. score:
8
Reversibility:
fully reversible
Irritant / corrosive response data:
The substance showed a primary irritation score of 0.00, when applied to healthy intact rabbit skin.
Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema.
No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.
Other effects:
No clinical signs of systemic toxicity were observed.
Light orange staining by the test article of the treated skin was observed.
The body weight gain of all rabbits was within the normal range of variability.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is classified as "not irritating" to rabbit skin.
Executive summary:

The primary skin irritation potential of the test article was investigated by Directive 92/69 EEC, B.4. "Acute Toxicity - Skin Irritation", July 31, 1992, U.S. Environmental Protection Agency, Code of Federal Regulations 40, Part 798, Health Effects Testing Guidelines, Subpart E, Specific organ/tissue toxicity, Paragraph 798.4470 "Primary dermal irritation", revised as of July 1, 1993, and OECD Guidelines for Testing of Chemicals, Section 4, number 404, "Acute Dermal Irritation / Corrosion", adopted July 17, 1992 (reported Paris April 29, 1993).

500 mg of the test item were topically applied onto 6 cm² intact dorsal skin of each of three young adult New Zealand rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then dividing by the number of

figures. Under the conditions of this experiment, the substance was found to cause a primary irritation score of 0.00 (max. 8.0) when applied to healthy intact rabbit skin. Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 edema. The test article caused light orange staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Based upon the referred classification criteria , the substance is classified as "not irritating" to rabbit skin.