Registration Dossier

Administrative data

Description of key information

The test substance was found to be corrosive to skin and causing irreversible damage to the eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1992-01-14 to 1992-02-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1984
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: T 16/91
- Expiration date of the lot/batch: July 1992
- Purity test date: 1992-05-13

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark
- Stability under test conditions: stable

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund
- Age at study initiation: about 3-5 months
- Weight at study initiation: 2700-3600 g
- Housing: single
- Diet: Altromin 2123 Haltungsdiat - Kaninchen, Altromin-GmbH (Lage/Lippe, Germany), ad libitum
- Water: deionized, chlorinated water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+/- 3
- Humidity (%): 55+/- 20
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
physiological saline
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 500 mg
- Concentration: ca. 90 %

VEHICLE
- Amount applied: 0,05 mL NaCl (0,9 %)
Duration of treatment / exposure:
3 minutes and 4 hours
Observation period:
Observations were caried out 30-60 min and 24, 48, 72 h, 7 days and 14 days after removal of the test substance.
Number of animals:
3 animals (3 min exposure)
1 animal (4 hours exposure)
Details on study design:
TEST SITE
- Area of exposure: dorsal, about 2.5 x 2.5 cm
- Type of wrap if used: semiocclusive

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing with tap water
- Time after start of exposure: 3 min or 4 h


OBSERVATION TIME POINTS
30-60min, 24 h, 48 h, 72 h, 7 days, 14 days

SCORING SYSTEM:
Erythema and edema were scored according to a 5 graded scale.
Irritation parameter:
erythema score
Remarks:
4 hours exposure
Basis:
animal #1
Remarks:
only one animal tested
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within:
Remarks:
14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
edema score
Remarks:
4 hours exposure
Basis:
animal #1
Remarks:
only one animal tested
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
positive indication of irritation
Irritation parameter:
erythema score
Remarks:
3 minutes exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
3 minutes exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Remarks:
3 minutes exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
3 minutes exposure
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
3 minutes exposure
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Remarks:
3 minutes exposure
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No signs of skin irritation were noticed after an exposure period of 3 minutes.
The animal exposed for 4 hours exhibited moderate to severe erythema at the observation time points 30-60 min, 24, 48, 72 h (score 3, respectively). At the observation time points 7 and 14 days the erythema were scored 4 (severe). Therefore, the findings were considered not reversible.
Edema were scored 3, 2, 1 and 1 at the time points 30-60 min, 24 h, 48 h and 72 hours and 1 after 7 and 14 days.
Other effects:
- Other adverse local effects: The skin appeared discoloured/white after 4 hours exposure. Further effects observed throughout the observation period: encrustation, scaled and dry skin.
Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
The test material was shown to be corrosive to skin after an exposure period of 4 hours.
Executive summary:

The test material was examined for its potential to cause skin irritation/corrosion in New Zealand White rabbits. 500 mg were diluted with 0.05 mL 0.9 % NaCl and applied under semiocclusive dressing. Three animals were exposed for 3 minutes, one animal was exposed for 4 hours. After removal of the patches the test sites were washed with tap water. Skin findings were scored 30-60 min, 24 h, 48 h, 72 h and 7 and 14 days after removal. No skin findings were noted in the animals exposed for 3 minutes. Signs of moderate to severe irritation were observed in the animal exposed for 4 hours. These findings were not reversible within the 14 days-observation period. Therefore the test item was concluded to be corrosive to skin.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1984-09-04 till 1984-09-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1981
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: VPS 11-ROM T3, technical grade material
- Purity test date: 1984-04-03

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the dark at 22 °C


Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund
- Weight at study initiation: 2200-3700 g
- Housing: single
- Diet: Altromin 2123 Haltungsdiät - Kaninchen, Altromin-GmbH (Lage/Lippe, Germany) ad libitum
- Water: deionized, chlorinated water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 2
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
- Concentration: ca. 71 %
Duration of treatment / exposure:
4 hours
Observation period:
Observations were caried out 30-60 min and 24, 48, 72 h and 7 days after removal of the test substance.
Number of animals:
3 animals (4 hours exposure)
Details on study design:
TEST SITE
- Area of exposure: dorsal to lateral, about 2.5 x 2.5 cm
- Type of wrap if used: semiocclusive

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
30-60min, 24 h, 48 h, 72 h, 7 days

SCORING SYSTEM:
Erythema and edema were scored according to a 5 graded scale.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 7d
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0.2
Max. score:
4
Reversibility:
fully reversible within: 48 h
Irritant / corrosive response data:
The animal exposed for 4 hours exhibited mild to moderate erythema at the observation time points 30-60 min, 24, 48, 72 h (score 1 or 2). After 7 days all erythema disappeared. Therefore, the findings were considered reversible.
Edema were scored 1 or 0 at the time points 24 h. On all other timepoints no edema were detected. Therefore, the findings were considered reversible.
Other effects:
- Other adverse local effects: The skin appeared dry after 72 hours exposure and dry and scaled after 7 days. After 14 days the skin appeared normal.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material is not considered to be classified as skin corrosive or irritant based on the test results..
Executive summary:

The test material (technical grade) was applied to the clipped skin of three New Zealand White rabbits. 0.5 mL were applied under semiocclusive dressing. The animals were exposed for 4 hours. After removal of the patches the test sites were washed. Skin findings were scored 30-60 min, 24 h, 48 h, 72 h and 7 and 14 days after removal. Signs of mild to moderate irritation were observed in the animal exposed for 4 hours, but hese findings were fully reversible within the 14 days-observation period. Therefore the test item (technical grade) was concluded to be not corrosive and not irritating to skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion:

The test material (at technical grade) was applied to the clipped skin of three New Zealand White rabbits. 0.5 mL were applied under semiocclusive dressing. The animals were exposed for 4 hours. After removal of the patches the test sites were washed. Skin findings were scored 30-60 min, 24 h, 48 h, 72 h and 7 and 14 days after removal. Signs of mild to moderate irritation were observed in the animal exposed for 4 hours, but hese findings were fully reversible within the 14 days-observation period. Therefore the test item (technical grade) was concluded to be not corrosive and not irritating to skin.

The test material was further examined for its potential to cause skin irritation/corrosion in another study with New Zealand White rabbits. 500 mg were diluted with 0.05 mL 0.9 % NaCl and applied under semiocclusive dressing. Three animals were exposed for 3 minutes, one animal was exposed for 4 hours. After removal of the patches the test sites were washed with tap water. Skin findings were scored 30-60 min, 24 h, 48 h, 72 h and 7 and 14 days after removal. No skin findings were noted in the animals exposed for 3 minutes. Signs of moderate to severe irritation were observed in the animal exposed for 4 hours. These findings were not reversible within the 14 days-observation period. Therefore the test item was concluded to be corrosive to skin.

Despite of the first study (only technical grade was used), the substance to be registered is considered to be classified as corrosive to skin.

Eye irritation/corrosion:

The local effect of the test item (at technical grade) was investigated according to the method recommended in the OECD Guideline No. 405. Three albino rabbits were exposed to 0.1 mL of the test article, applicated undiluted in one eye. The eyes were examined and the changes were graded according to a numnerical scale one hour, 24, 48 and 72 hours after dosing. Additional examinations were conducted after 7 and 14 days. The local effect of the test item was investigated according to the method recommended in the OECD Guideline No. 405. Three albino rabbits were exposed to 0.1 mL of the test article, applicated undiluted in one eye. The eyes were examined and the changes were graded according to a numnerical scale one hour, 24, 48 and 72 hours after dosing. Additional examinations after 7 and 14 days. From 1 hour after application onwards chemosis was observed, which increased over time in all test animals. It was not possible to assess the conjunctivae score due to a whitish discolouration of the conjunctivae and nicitating membranes. Cornea opacity was observed in all treated eyes from 1 hour p.a. onwards, reversibility could not be assessed as in one animal the application led to destruction of the complete eyeball on day 7, in the remaining two animals on day 14. In conclusion the test item causes serious eye damage (Category 1).

 

Although the study was conducted with the test material of lower purity (technical grade) no further testing is required as besides this in vivo eye irritation study the results from the skin irritation study with the pure test material already triggers classification as corrosive to skin and causing irreversible damage to the eyes.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified as corrosive to skin (cat 1C) and labelled with H314: 'Causes severe skin burns and eye damage' under Regulation (EC) No 1272/2008, and as corrsosive to the eyes (cat 1) and lebaled with H318: 'Causes serious eye damage' as amended for the tenth time in Regulation (EU) No 2017/776.