Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin corrosion: The test item is corrosive to skin because the key study demonstrated that occluded contact with the substance for one hour produced severe irritation (erythema scores at 24/48/72 hours ≥ 2.3 in 5/6 animals) and necrosis was observed in three of the six animals within 7 days (US D.O.T regulations and OECD 404). These data were replicated in a supporting study (US D.O.T regulations and OECD 404).

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:
key study
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: Department of Transportation, Method of Testing Corrosion to Skin
Version / remarks:
Federal Register, Vol 41, No 118, Sept 27 1976
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Remarks:
albino
Details on test animals or test system and environmental conditions:
ANIMALS AND ANIMAL HUSBANDRY
- Rabbits were sourced from Kuiper Rabbitry, Gary, Indiana, USA and were approximately 8-10 weeks old.
- Animals were housed individually in stainless steel cages in a temperature, humidity and light controlled room.
- Rabbits were conditioned for at least three days prior to study initiation.
- Purina Rabbit Chow and water were available ad libitum.
- All animals used for the investigation were considered to be in good health at study initiation.
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
3 minutes, 1 hour and 4 hours
Observation period:
7 days
Number of animals:
Six
Details on study design:
COMPOUND ADMINISTRATION
- Three intact sites were prepared on each of the six animals.
- A dose of 0.5 mL of the test article was applied to the occluded sites for contact periods of 3 minutes (site A), 1 hour (site B) and 4 hours (site C).
- At the conclusion of the individual contact periods, any remaining test material was wiped from the site.
- If necrosis was observed at the shorter contact periods the test was considered to be concluded and longer exposure times were not required.

CLINICAL OBSERVATIONS
- Observations for irritation, ulceration and necrosis were performed at the end of each contact period.
- Observations were repeated at 60 minutes for the 3 minute contact time.
- Observations were repeated at 24, 48 and 72 hours following test article application for the 1 and 4-hour contact times.
- Additional readings were continued up to Day 7 to confirm transport packing group
- Corrosion was considered to have resulted if the substance in contact with rabbit skin produced full thickness destruction or irreversible alteration of tissue.
- Tissue destruction was considered to have occurred if ulceration and/or necrosis was observed at any of the readings.
- Tissue destruction did not include merely sloughing of the epidermis, erythema, edema or fissuring.
- Scoring crieria used during evaluation of skin reactions are given in Table 2 (attached).
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 min contact time
Time point:
other: 3 min
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks:
site A
Remarks on result:
other:
Remarks:
Animals 53, 54, 55, 56, 57 and 58
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 min contact time
Time point:
other: 1 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks:
site A
Remarks on result:
other: not corrosive after 3 min contact time
Remarks:
Animals 53, 54, 55, 56, 57 and 58
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks:
site B
Remarks on result:
other: Animal 53
Remarks:
Necrosis reported at 7 d observation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
site B
Remarks on result:
other: Animal 54
Remarks:
Score unchanged at 7 d observation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks:
site B
Remarks on result:
other: Animal 55
Remarks:
Necrosis reported at 72 h observation
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
site B
Remarks on result:
other: Animal 56
Remarks:
Score unchanged at 7 d observation
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks:
site B
Remarks on result:
other: Animal 57
Remarks:
Score unchanged at 7d observation
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: Animal 58
Remarks:
Necrosis reported at 7 d observation
Irritant / corrosive response data:
- Data showing individual responses of each animal are attached.
- Occluded contact with the test material for three minutes produced no irritation and necrosis was not observed in any of the six animals.
- Occluded contact with the test material for one hour produced severe irritation and necrosis was observed in three of the six animals within 7 days.
- Occluded contact with the test material for four hours caused necrosis in all six animals.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Occluded contact with the test item for one hour produced severe irritation (erythema scores at 24/48/72 hours ≥ 2.3 in 5/6 animals) and necrosis was observed in three of the six animals within 7 days. On the basis of this study, the test material is found to be corrosive to skin.
Executive summary:

In a study performed in accordance with US D.O.T. regulations and OECD 404, the test item was applied to three prepared skin sites on New Zealand White rabbits under occluded conditions for 3 minutes, 1 hour and 4 hours. After the relevant contact period, any remaining test item was wiped from the site. After removal of patches and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored for erythema. No effects were noted over a period of 60 minutes following contact with the test item for 3 minutes. However, occluded contact with the test item for one hour produced severe irritation (erythema scores at 24/48/72 hours ≥ 2.3 in 5/6 animals) and necrosis was observed in three of the six animals within 7 days. On the basis of this study, the test material is found to be corrosive to skin.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: Department of Transportation, Method of Testing Corrosion to Skin
Version / remarks:
Federal Register, Vol 41, No 118, Sept 27 1976
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Remarks:
albino
Details on test animals or test system and environmental conditions:
ANIMALS AND ANIMAL HUSBANDRY
- Rabbits were sourced from Kuiper Rabbitry, Gary, Indiana, USA and were approximately 8-10 weeks old.
- Animals were housed individually in stainless steel cages in a temperature, humidity and light controlled room.
- Rabbits were conditioned for at least three days prior to study initiation.
- Purina Rabbit Chow and water were available ad libitum.
- All animals used for the investigation were considered to be in good health at study initiation.
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
3 minutes, 1 hour and 4 hours
Observation period:
7 days
Number of animals:
Six
Details on study design:
COMPOUND ADMINISTRATION
- Three intact sites were prepared on each of the six animals.
- A dose of 0.5 mL of the test article was applied to the occluded sites for contact periods of 3 minutes
(site A), 1 hour (site B) and 4 hours (site C).
- At the conclusion of the individual contact periods, any remaining test material was wiped from the site.
- If necrosis was observed at the shorter contact periods the test was considered to be concluded and
longer exposure times were not required.

CLINICAL OBSERVATIONS
- Observations for irritation, ulceration and necrosis were performed at the end of each contact period.
- Observations were repeated at 60 minutes for the 3 minute contact time.
- Observations were repeated at 24, 48 and 72 hours following test article application for the 1 and 4-
hour contact times.
- Additional readings were continued up to Day 7 to confirm transport packing group
- Corrosion was considered to have resulted if the substance in contact with rabbit skin produced full thick
ness destruction or irreversible alteration of tissue.
- Tissue destruction was considered to have occurred if ulceration and/or necrosis was observed at any of
the readings.
- Tissue destruction did not include merely sloughing of the epidermis, erythema, edema or fissuring.
- Scoring crieria used during evaluation of skin reactions are given in Table 2 (attached).
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 min contact time
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not reversible
Remarks:
site A
Remarks on result:
other: Animals 49, 50, 51, 53 and 54
Remarks:
Score was 3 at 7 d observation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
3 min contact time
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
not reversible
Remarks:
site A
Remarks on result:
other: Animal 52
Remarks:
Score was 3 at 7d observation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Remarks:
site B
Remarks on result:
other: Animals 50, 51 and 54
Remarks:
Score was 4 at 7 d observation
Irritation parameter:
erythema score
Basis:
mean
Remarks:
1 h contact time
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not reversible
Remarks:
site B
Remarks on result:
other: Animals 49, 52 and 53
Remarks:
Necrosis was reported at 7 d observation
Irritant / corrosive response data:
- Data showing individual responses of each animal are attached.
- Occluded contact with the test material for three minutes produced moderate to severe irritation in all six animals tested. However, necrosis and irreversible damage were not seen.
- Occluded contact with the test material for one hour produced severe irritation in all six animals. Necrosis and full thickness damage was observed in three of the six animals within 7 days.
- Occluded contact with the test material for four hours caused severe irritation in all six animals. Necrosis and full thickness damage was observd in five out of the six animals within 7 days.
Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Severe irreversible skin irritation (6/6 animals) was reported after contact with the test item for 3 minutes and severe skin irritation (6/6 animals) followed by necrosis (3/6 animals) was observed following occluded contact with the test material for one hour.
Executive summary:

In a study performed in accordance with US D.O.T. regulations and OECD 404, the test item was applied to three prepared skin sites on New Zealand White rabbits under occluded conditions for 3 minutes, 1 hour and 4 hours. After the relevant contact period, any remaining test item was wiped from the site. After removal of patches and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored for erythema. Severe irreversible skin irritation was reported after contact with the test item for 3 minutes (erythema scores ≥ 2.3 in 6/6 animals persisting to the 7 d observation when the score attributed to each animal was 3). Contact with the test item for one hour produced severe irritation (erythema scores at 24/48/72 hours ≥ 2.3 in 6/6 animals) and necrosis was observed in three of the six animals within 7 days. On the basis of this study, the test material is found to be corrosive to skin.

Endpoint:
skin corrosion: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study need not be conducted because the available information indicates that the criteria are met for classification as corrosive to the skin or irritating to eyes
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)
Endpoint:
eye irritation: in vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as skin corrosion, leading to classification as serious eye damage (Category 1)
Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin corrosion: In a key study performed in accordance with US D.O.T. regulations and OECD 404, the test item was applied to three prepared skin sites on New Zealand White rabbits under occluded conditions for 3 minutes, 1 hour and 4 hours. After the relevant contact period, any remaining test item was wiped from the site. After removal of patches and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored for erythema. No effects were noted over a period of 60 minutes following contact with the test item for 3 minutes. However, occluded contact with the test item for one hour produced severe irritation (erythema scores at 24/48/72 hours ≥ 2.3 in 5/6 animals) and necrosis was observed in three of the six animals within 7 days. On the basis of this study, the test material is found to be corrosive to skin. In a supporting study, conducted in accordance with the same test guidelines, severe irreversible skin irritation was reported after contact with the test item for 3 minutes (erythema scores ≥ 2.3 in 6/6 animals persisting to the 7 d observation when the score attributed to each animal was 3). Contact with the test item for one hour produced severe irritation (erythema scores at 24/48/72 hours ≥ 2.3 in 6/6 animals) and necrosis was observed in three of the six animals within 7 days. This study provides confirmation that the test material is corrosive to skin.

Justification for classification or non-classification

Skin corrosion: The results of two studies reported corrosive responses in at least one animal following exposure > 3 min and ≤ 1 h with observations ≤ 14 days. Classification as Skin Corr 1B is therefore warranted under the terms of Regulation (EC) No 1272/2008.