Registration Dossier

Administrative data

Description of key information

The submission item was determined to be corrosive in a primary dermal irritation study.  No eye irritation test was performed in accordance with Regulation (EC) 1907/2006, column 2 of Annex VIII. However, according to CLP regulation skin corrosive substances are considered as leading to serious damage of the eyes as well (category 1)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004-03-12 To: 2004-06-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, Guidline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Gauze square were not protected by a pad and not held in place by elastic, adhesive hypoalergenic tape. Deviation does not affect study outcome
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: GEVAC (Les Hautes Noes, Saint Mars d'Egrenne, 61350 Passais la conception, France)
- Weight at study initiation: 3.5 kg
- Housing: individually, in standard size cage
- Diet: SDS/DIETEXnSTANRAB (P) SQC ad libitum
- Water: ad libitum
- Acclimation period: 5 days prior to testing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21°C
- Humidity (%): 45-65%
- Air changes (per hr): 10 times/hour
- Photoperiod (hrs dark / hrs light): 12712

IN-LIFE DATES: From: 2004-03-23 To: 2004-03-26
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle used
Duration of treatment / exposure:
3 minutes exposure
1 h exposure
4 h exposure
Observation period:
1h (where appropriate), 24, 48 and 72 hours post exposure
Number of animals:
1 female rabbit
Details on study design:
TEST SITE
- Area of exposure: 6 cm2 per patch
- % coverage: no data
- Type of wrap if used: gauze, semiocclusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no
- Time after start of exposure: up to 4h

SCORING SYSTEM:
Erythema and eschar formation
No erythema: 0
Very slight erythema (Barely discernable): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beat redness) to scab formation hindering classification based on erythema: 4

Oedema formation
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure): 4
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4h exposure
Time point:
other: 1h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 h exposure
Time point:
other: 4 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 h exposure
Time point:
other: 72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 h exposure
Time point:
other: 24 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 h exposure
Time point:
other: 1 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 h exposure
Time point:
other: 24 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 h exposure
Time point:
other: 48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 h exposure
Time point:
other: 72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritant / corrosive response data:
Mean index(Mi)

3 min exposure: mean erythema 3.33 / mean oedema 4.0
1 h exposure: mean erythema 3.33 / mean oedema 4.0
24 h exposure: mean erythema 3.67 / mean oedema 3.67
Other effects:
At time point 24 h and 48 h after removal of patches green and brown colouration of each site appeared. These zones were surrounded with an erythemateous zone.
At time point 72h the additinally skin suppleness decreased and necrosis was noted.
Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance is corrosive to the skin. Necrosis, destruction of the skin appeared later than 48h observation.
CPL Classification Category 1B is proposed
Executive summary:

Primary dermal irritation study was performed with MXDA/SM Adduct in accordance with OECD guideline No. 404 (1981).

The test substancewas applied to three different sites topically dermal (approximately 6 cm2) on the back of the one New Zealand White rabbit for 3 minutes (one patch), 1 hour (second patch) and 4 hours (third patch) of exposure. After completion of the exposure period the treated areas were observed after 1h, 24 h, 48 h and 72 h post exposure.

Moderate to severe erythema (Score 3 -4) and odema (Score 3-4) were noted at all three application sites after 24 until 72 h post exposure. At time point 24 h and 48 h after removal of patches green and brown colouration of each site appeared. These zones were surrounded with an erythemateous zone. At time point 72h the additinally skin suppleness decreased and necrosis was noted.

Based on the result above, the test material was decided to be a corrosive material.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A primary dermal irritation study was performed in accordance with OECD TG 404. The submission item was dermally applied to one rabbit at three different application sites for 3 minuets (one patch), 1hour (second patch) and 4 hours (third patch) of exposure. After completion of the exposure period the treated areas was observed for up to 72 hours. Moderate to severe erythema (Score 3 -4) and odema (Score 3-4) were noted at all three application sites after 24 hours until 72 hours post exposure. At time point 24 h and 48 h after removal of patches green and brown colouration of each site appeared. These zones were surrounded with an erythemateous zone. At time point 72h the additinally skin suppleness decreased and necrosis was noted.

Based on the result above, the test material was decided to be a corrosive material.

As the submission item was determined to be corrosive in the skin irritation test, no eye irritation test was performed in accordance with Regulation (EC) 1907/2006, column 2 of Annex VIII.


Justification for selection of skin irritation / corrosion endpoint:
Klimisch 1, guideline and GLP-conform study. This sutdy is supported by hte non-GLP study Harada, 2002.

Justification for selection of eye irritation endpoint:
The test item is corrosive to the skin.

Effects on skin irritation/corrosion: corrosive

Justification for classification or non-classification

The submission item was determined to be corrosive in a dermal irritation study. Corrosive effects were reported after 3 minutes to 4 hours of exposure after 48 h observation time.

Regulation (EC) No 1272/2008 (CLP): Skin corrosion category 1B, H314 “Causes severe skin burns and eye damage”.

Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC): C; R34 "Causes burns”.

No eye irritation test was performed, as skin corrosiveness automatically implies corrosiveness to the eye.