Registration Dossier

Administrative data

Description of key information

In a GLP compliant OECD TG 404 study, the test item was investigated for skin irritation / corrosion properties in rabbits. Based on the results, the registration substance is considered to be corrosive to skin. Likewise, testing according to OECD TG 405 revealed that the registration substance is severely irritating to eyes. No data with regard to respiratory irritation is available. However, due to the corrosive nature, respective exposure has to be minimized.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
At this time an In-vivo study was performed and therefore covers this endpoint.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD Guideline 404.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Hoechst AG, conventional breeding- Age at study initiation: 3 - 5 month- Weight at study initiation: 2.7 - 3.3 kg- Housing: individual in stainless steel cages- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: at least 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 +/- 3°C- Humidity (%): 50 +/- 20 %- Air changes (per hr): 15- Photoperiod (hrs dark / hrs light): 12 hour interval
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL of undiluted test item
Duration of treatment / exposure:
1 hour respectively 4 hours
Observation period:
The evaluation was carried out 30 - 60 min and 24, 48 and 72 hours as well as 7, 14 and 21 days after the removal of the patch.
Number of animals:
1 hour of exposure: 3 animals4 hours of exposure: 3 animals
Irritation parameter:
erythema score
Remarks:
1 hour exposure
Basis:
mean
Remarks:
all animals
Time point:
other: 24 / 48 / 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Remarks:
1 hour exposure
Basis:
animal #1
Remarks:
mean
Time point:
other: 24 / 48 / 72 hours
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
erythema score
Remarks:
1 hour exposure
Basis:
animal #2
Remarks:
mean
Time point:
other: 0.67
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Remarks:
1 hour exposure
Basis:
animal #3
Remarks:
mean
Time point:
other: 24 / 48 / 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Remarks:
1 hour exposure
Basis:
mean
Remarks:
all animals
Time point:
other: 24 / 48 / 72 hours
Score:
0.1
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Remarks:
1 hour exposure
Basis:
animal #1
Remarks:
mean
Time point:
other: 24 / 48 / 72 hours
Score:
0.1
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Remarks:
1 hour exposure
Basis:
animal #2
Remarks:
mean
Time point:
other: 24 / 48 7 72 hours
Score:
0
Max. score:
0
Irritation parameter:
edema score
Remarks:
1 hour exposure
Basis:
animal #3
Remarks:
mean
Time point:
other: 24 / 48 / 72 hours
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Remarks:
4 hour exposure
Basis:
mean
Remarks:
all animals
Time point:
other: 24 / 48 / 72 hours
Score:
2.44
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
erythema score
Remarks:
4 hour exposure
Basis:
animal #1
Remarks:
mean
Time point:
other: 24 / 48 / 72 hours
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
erythema score
Remarks:
4 hour exposure
Basis:
animal #2
Remarks:
mean
Time point:
other: 24 / 48 / 72 hours
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
erythema score
Remarks:
4 hour exposure
Basis:
animal #3
Remarks:
mean
Time point:
other: 24 / 48 / 72 hours
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
edema score
Remarks:
4 hour exposure
Basis:
mean
Remarks:
all animals
Time point:
other: 24 / 48 / 72 hours
Score:
0.67
Max. score:
2
Reversibility:
fully reversible
Remarks:
14 days
Irritation parameter:
edema score
Remarks:
4 hour exposure
Basis:
animal #1
Remarks:
mean
Time point:
other: 24 / 48 / 72hours
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Remarks:
4 hour exposure
Basis:
animal #2
Remarks:
mean
Time point:
other: 24 / 48 / 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Remarks:
4 hour exposure
Basis:
animal #3
Remarks:
mean
Time point:
other: 24 / 48 / 72hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
4 hour exposure: Scare formation in one animal, no full revesibility in all animals after 21 days
Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the test results of this study, the test material is considered to be corrosive to rabbit skin.
Executive summary:

The registration substance was tested in a GLP conform study for skin irritation / corrosion according to OECD test guideline 404. For this 0.5 mL of undiluted test material was applied semi-occlusively for 1 hour or 4 hours to the shaved skin of three New Zealand White rabbits per exposure period. The skin then was examined 30 minutes, 1 hour, 24, 48 and 72 hours after removal of the dressing. Since effects were still present after 72 hours, additional readings were performed after 7, 14 (1 hour exposure group) and 21 days (4 hour exposure group).

Results for the 60 minute exposure period (3 animals): From 30 minutes to 14 days after patch removal, the treated skin sites showed mild to moderate erythema and mild to strong oedema. Between 24 hours and 14 days, the treated skin areas were cracked, dry-brittle, and scaly. Additionally scaling was observed. All signs of irritation were reversible.

Results for the 4 hour exposure period (3 animals): From 30 minutes to 21 days after application, the skin was temporarily sclerotic, vaulted, encrusted, scabby, white and brown-white discoloured. Additionally, skin induration was noted in two animals 21 days post exposure. In the remaining animal full thickness destruction of the epidermis occurred after 21 days.

Based on the results of this study, the test item was corrosive to rabbit skin.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation, other
Remarks:
At this time a In-vivo study was performed and therefore covers this endpoint.
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: According to OECD Guideline 405.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS- Source: Hoechst AG, conventional breeding- Age at study initiation: 3 - 5 month- Weight at study initiation: 3.5 - 3.8 kg- Housing: individual in stainless stell cages- Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum): ad libitum- Acclimation period: at least 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 20 +/-3°C- Humidity (%): 50 +/- 20 %- Air changes (per hr): 15- Photoperiod (hrs dark / hrs light): 12 hour interval
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL of the undiluted test item
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
24 hours (due to severe eye irritation reactions study was terminated after this reading)
Number of animals or in vitro replicates:
3
Details on study design:
24 hours in advance to the study, the later tested eye of each rabbit was treated with fluoresceine Na-salt (0.01%) in order to check the cornea concerning defects. Only animals without diagnostic findings regarding the cornea were choosen for further testings.For the study 0.1 mL of the test item (concentration is 78 %; composition reported in confidential details on test material) was applied to the conjunctival sac of the left eye of each testing animal. The non treated eye served as control eye.Damages on the cornea, the iris and on the conjunctiva were numerical evaluated. All other changes were also recorded.
Irritation parameter:
cornea opacity score
Remarks:
all animals
Basis:
mean
Remarks:
over all
Time point:
other: 24 hours
Score:
4
Max. score:
4
Reversibility:
other: study terminated due to the severity of findings
Irritation parameter:
iris score
Remarks:
all animals
Basis:
mean
Remarks:
overall
Time point:
other: 24 hours
Remarks on result:
other: not assessable due to severe opacity of cornea
Irritation parameter:
conjunctivae score
Remarks:
all animals
Basis:
mean
Remarks:
overall
Time point:
other: 24 hours
Score:
3
Max. score:
3
Reversibility:
other: study terminated due to severity of findings
Irritation parameter:
chemosis score
Remarks:
all animals
Basis:
mean
Remarks:
over all
Time point:
other: 24 hours
Score:
4
Max. score:
4
Reversibility:
other: study terminated due to severity of findings
Irritant / corrosive response data:
At the 24 hour reading severe eye irritation in form of opaque cornea, non assessable iris and severe chemosis including white discoloration of conjunctivae occurred. Based hereupon the study was terminated and the animals humanly killed.
Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the study results, the test material is considered to be severly irritating to rabbit eyes.
Executive summary:

In an OECD TG 405 study, 0.1 ml of the test material was applied to the eye of 3 New Zealand White rabbit. From 1 hour onwards, the conjunctiva showed red beefy discoloration and pronounced chemosis. The cornea exhibited opalescent areas or was opaque with no details of the iris visible. Because these lesions had progressed at the 24 hour reading, the study was terminated and the animals humanly killed for animal welfare reasons. Accordingly, the test item has to be considered as severely irritating to eyes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The registration substance was tested in a GLP conform study for skin irritation / corrosion according to OECD test guideline 404. For this 0.5 mL of undiluted test material was applied semi-occlusively for 1 hour or 4 hours to the shaved skin of three New Zealand White rabbits per exposure period. The skin was examined 30 minutes, 1 hour, 24, 48 and 72 hours after removal of the dressing. Since effects were still present after 72 hours, additional readings were performed after 7, 14 (1 hour exposure group) and 21 days (4 hour exposure group). Results for the 60 minute exposure period (3 animals): From 30 minutes to 14 days after patch removal, the treated skin sites showed mild to moderate erythema and mild to strong oedema. Between 24 hours and 14 days, the treated skin areas were cracked, dry-brittle, and scaly. Additionally scaling was observed. Results for the 4 hour exposure period (3 animals): From 30 minutes to 21 days after application, the skin was temporarily sclerotic, vaulted, encrusted, scabby, white and brown-white discoloured. Additionally, skin induration was noted in two animals 21 days post exposure. In the remaining animal full thickness destruction of the epidermis occurred after 21 days. Based on the results of this study, the test item was corrosive to rabbit skin.

In an OECD TG 405 study, 0.1 ml of the test material was applied to the eye of 3 New Zealand White rabbit. From 1 hour onwards, the conjunctiva showed red beefy discoloration and pronounced chemosis. The cornea exhibited opalescent areas or was opaque with no details of the iris visible. Because these lesions had progressed at the 24 hour reading, the study was terminated and the animals humanly killed for animal welfare reasons. Accordingly, the test item has to be considered as severely irritating to eyes.


Justification for selection of skin irritation / corrosion endpoint:
Guideline study according to GLP with a Klimisch rating 1.

Justification for selection of eye irritation endpoint:
Guideline study according to GLP with a Klimisch rating 1.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the results of guideline conform testing, the registration substance has to be considered as skin corrosive and is classified as `skin corrosive` subcategory 1C with the designation H314 - causes severe skin burns and eye damage according to GHS-CLP (equivalent to EU risk phrase `R34 - causes burns` according to DSD)