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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From June 11th to 14h, 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
April 24, 2002
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
June 16, 2004
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
August 1998
Qualifier:
according to guideline
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
Basic Blue 140
IUPAC Name:
Basic Blue 140

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Centre Lago S. A., 01540 Vonnas, France.
- Age at study initiation: 5 - 8 months.
- Weight at study initiation: 3.60 - 4.80 kg.
- Housing: single housing, stainless steel wire mesh cages with grating, floor area: 3000 cm².
- Diet: Kliba-Labordiät about 130 g/animal per day.
- Water: tap water. ad libitum.
- Acclimation period: at least 5 days before application. Before the beginning of application, the application area was investigated for signs of pre-existing skin irritation or dense patches of hair. Only animals with intact healthy skin were used.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 – 24 °C
- Humidity: 30 - 70 %
- Photoperiod: 12 hrs dark / 12 hrs light

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Remarks:
doubly distilled
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g
- Preoparation: the solid test substance was minimally moistened with a suitable amount of doubly distilled water to guarantee skin contact immediately before test-substance application. Because of the natural moisture of the skin doubly distilled water was used for moistening, so that the test was carried out under conditions as physiological as possible.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 rabbits: 2 males, 1 female
Details on study design:
TEST SITE
- Area of exposure: at least 24 hours before application clipping of the dorsolateral part of the trunk of the animal(s).
- Type of coverage: the test patch (2.5 x 2.5 cm) was secured in position with a semiocclusive dressing (Idealbinde, Pfälzische Verbandstoff-Fabrik,Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AG).

REMOVAL OF TEST SUBSTANCE
- Washing: the test substance was removed at the end of the exposure period with Lutrol®and Lutrol® / water (1 : 1) (Lutrol® E 400 = Polyethylenglycol, BASF Aktiengesellschaft).
- Time after start of exposure: 4 hours.

OBSERVATIONS
- Readings: Immediately after removal of the patch, approx. 1, 24, 48 and 72 h after removal of the patch and then in weekly intervals maximally up to day 14.
- Illumination used for reading: daylight tubes "Lumilux" (L 58W/860 PLUS ECO 25X1, Osram, Germany).
- Mortality: a check for any dead or moribund animal was made twice each workday (at the beginning and end of work) and once daily at weekends and on public holidays.
- Body weight determination: just before application of the test substance and after the last reading.

SCORING SYSTEM
The evaluation of skin reactions was performed according to the quoted guidelines. For evaluation, the calculation of the mean values of erythema and edema for readings at 24, 48 and 72 hours were quoted. Additionally, the reversibility of the observed findings was taken into account. The evaluation is based on the criteria of the Commission Directive 67/548/EEC and the OECD Harmonized Integrated Classification System that were in place on the date of report signature.

Erythema and eschar formation - Grading
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to eschar formation preventing grading of erythema

Edema formation - Grading
0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well defined by definite raising)
3 Moderate edema (raised approx. 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: 3/3
Time point:
24/48/72 h
Score:
< 2.3
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal: 3/3
Time point:
24/48/72 h
Score:
< 2.3
Reversibility:
fully reversible
Irritant / corrosive response data:
Moderate erythema (grade 2) was observed in all animals immediately and 1 hour after removal of the patch and persisted in one animal up to 24 hours. Moderate erythema decreased to slight (grade 1) in two animals after 24 hours and in one animal after 48 hours.
Slight erythema persisted in one animal up to 48 hours.
The cutaneous reactions were reversible in one animal within 48 hours and in two animals within 72 hours after removal of the patch.
Mean scores over 24, 48 and 72 hours for each animal were 0.3, 1.0 and 0.7 for erythema and 0.0 for edema.

Any other information on results incl. tables

Reaciton Readings (hours) Mean 24, 48 and 72 hrs
Animal 0 1 24 48 72
Erythema Animal 01 (M) 2 2 1 0 0 0.3
Animal 02 (M) 2 2 2 1 0 1.0
Animal 03 (F) 2 2 1 1 0 0.7
Oedema Animal 01 (M) 0 0 0 0 0 0.0
Animal 02 (M) 0 0 0 0 0 0.0
Animal 03 (F) 0 0 0 0 0 0.0

Applicant's summary and conclusion

Interpretation of results:
other: not classified, according to the CLP Regulation (EC 1272/2008)
Conclusions:
Not irritating
Executive summary:

The potential of the test substance to cause acute skin irritation was assessed according to the OECD guideline 404. Intact skin of 3 White New Zealand rabbits was exposed to 0.5 g of the test substance in a single topical application for 4 hours. A patch of 2.5 cm x 2.5 cm, covered with semiocclusive dressing was used. After removal of the patch, the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch. Slight or moderate erythema were observed in all animals during the course of the study. The cutaneous reactions were reversible in all animals within 72 hours after removal of the patch.

The average score (24 to 72 hours) for irritation was calculated to be 0.7 for erythema and 0.0 for edema. Considering the described cutaneous reactions as well as the average score for irritation, the test substance does not show a skin irritation potential under the test conditions chosen.

Discussion and conclusion

Mean values from gradings at 24, 48 and 72 hours after patch removal were lower than 2.3 in all animals for both erythema/eschar and oedema reactions, thus the test item does not meet the criteria to be classified as irritating, according to the CLP Regulation (EC 1272/2008).