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Administrative data

Description of key information

The test item is considered to be a corrosive to the ocular tissue of the rabbit.

The test item is considered to be a corrosive to the skin of the rabbit.

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:
from 1996-06-04 to 1996-08-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Lot No.: 0998603612
Purity: 59.6 %
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Myrtle's Rabbitry, Thompson Station, TN, USA
- Age at study initiation: adult
- Weight at study initiation: approximately 2.0 to 3.5 kg
- Housing: individually in suspended stainless steel cages
- Diet: PMI Certified Rabbit Chow #5322 (Purina Mills, Inc.) was provided ad libitum to the animals throughout the study.
- Water: Municipal tap water treated by reverse osmosis was available ad libitum throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.9 - 21.7 °C (66 - 71 °F)
- Humidity (%): 56 - 78
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g / 100 % concentration
Duration of treatment / exposure:
4 hours
Observation period:
up to 14 days after removing the gauze
Number of animals:
6 males
Details on study design:
TEST SITE
- Area of exposure: the dorsal area of the trunk
- % coverage: approximately 1 inch x 1 inch
- Type of wrap: 1 x 1 inch square 4-ply gauze patch

REMOVAL OF TEST SUBSTANCE
- Washing: after 4 hours of exposure; cleaned with wet gauze and then with dry
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
1, 24, 48 and 72 hours up to 14 days after patch removal

SCORING SYSTEM:
- Method of calculation: Macroscopic Dermal Grading System based on Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
probability of severe irritation
Remarks:
injuries in depth
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
probability of severe irritation
Remarks:
injuries in depth
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
probability of severe irritation
Remarks:
injuries in depth
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
3.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
probability of severe irritation
Remarks:
injuries in depth
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.6
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
probability of severe irritation
Remarks:
injuries in depth
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
probability of severe irritation
Remarks:
injuries in depth
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
Exposure to the test article produced moderate edema and moderate to severe blanching on 6/6 test sites at the 1 hour scoring interval. Additional dermal findings of eschar exfoliation and desquamation which were noted on 4/6 and 5/6 test sites, respectively and apparent necrosis and eschar which were noted on 6/6 test sites. The dermal irritation resolved completely in 1/6 animals by study day 14.
Under the conditions of this test, the test item is considered to be a corrosive to the skin of the rabbit.
Other effects:
Apparant necrosis in different formations were observed.

As the observed erythema effect were more severe than the scorring scale allows to be classified, an additional score was added M-4 (= 5) which represented the most severely affected areas - injuries in depth. When this score was assigned additionally the type of injuries were described.

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Conclusions:
It was determined that the test item corrosive to skin.
Executive summary:

The potential irritant and/or corrosive effects of the test item were evaluated on the skin of New Zealand White rabbits in a study performed according to OECD 404, EC Regulation 124/92 method B.4 and EPA OPPTS 798.4470. Each of six rabbits received a 0.5 g dose of the test article as a single dermal application. The dose was held in contact with the skin under a semi-occlusive binder for an exposure period of four hours. Following the exposure period, the binder was removed and the remaining test article was wiped from the skin using gauze moistened with distilled water followed by dry gauze. Test sites were subsequently examined and scored for dermal irritation for up to 14 days following patch removal.

Exposure to the test article produced moderate edema and moderate to severe blanching on 6/6 test sites at the 1 hour scoring interval. Additional dermal findings included eschar exfoliation and desquamation which were noted on 4/6 and 5/6 test sites, respectively, and apparent necrosis and eschar which were both noted on 6/6 test sites. The dermal irritation resolved completely in 1/6 animals by study day 14.

Under the conditions of this test, the test item is considered to be a corrosive to the skin of the rabbit.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 1996-06-07 to 1996-08-29
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Lot No.: 0998603612
Purity: 59.6 %
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Myrtle's Rabbitry, Thompson Station, TN, USA
- Age at study initiation: adult
- Weight at study initiation: approximately 2.0 to 3.5 kg
- Housing: individually in suspended stainless steel cages
- Diet: PMI Certified Rabbit Chow #5322 (Purina Mills, Inc.) was provided ad libitum to the animals throughout the study.
- Water: Municipal tap water treated by reverse osmosis was available ad libitum throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 - 20 °C (67 - 68 °F)
- Humidity (%): 62 - 85
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
100 % concentration; 0.1 g substance were instilled
Duration of treatment / exposure:
Single dosage with no rinse.
Observation period (in vivo):
72 h
Number of animals or in vitro replicates:
1 female rabbit
Details on study design:
The test article was instilled into the conjunctival sac of the right eye of the animal after gently pulling the lower lid away from the eye. Following instillation, the eyelids were gently held together for approximately one second in order to limit test article loss and the animal was returned to its cage. The contralateral eye remained untreated to serve as a control.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
48 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
2
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
48 h
Max. score:
2
Remarks on result:
not determinable
Remarks:
due to degree of opacity
Irritation parameter:
iris score
Basis:
animal #1
Time point:
72 h
Max. score:
2
Remarks on result:
not determinable
Remarks:
due to degree of opacity
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: conjunctival redness
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: conjunctival redness
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: conjunctival redness
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: conjunctival swelling
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: conjunctival swelling
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: conjunctival swelling
Irritant / corrosive response data:
Exposure to the test article produced corneal opacity in the test eye at the 1 hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24 hour scoring interval. Iritis was observed in the test eye at the 1 hour scoring interval. Conjunctivitis (redness and swelling) was noted in the test eye at the 1 hour scoring interval. Additional ocular findings of blanching of nictating membrane, blanching of conjunctival tissue, ocular discharge-yellow and head tilt were noted in the test eye. Due to the severe irritation noted, the animal was euthanized following the 72 hour score.
No corneal opacity, iritis or conjunctivitis was observed in the control eyes.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Based on the initial rabbit dosed, the test item is considered to be a corrosive to the ocular tissue of the rabbit.
Executive summary:

The potential irritant and/or corrosive effects of the test item were evaluated on the eyes of New Zealand White rabbits. One rabbit received a 0.1000 g (0.1 mL weight equivalent) dose of the test item in the conjunctival sac of the right eye. The contralateral eye of the animal remained untreated and served as a control. The test and control eye was examined for signs of irritation for up to 72 hours following dosing. Due to the amount of irritation noted in the initial rabbit, the remaining animals were not dosed.

Exposure to the test article produced corneal opacity in the test eye at the 1 hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24 hour scoring interval. Iritis was observed in the test eye at the 1 hour scoring interval. Conjunctivitis (redness and swelling) was noted in the test eye at the 1 hour scoring interval. Additional ocular findings of blanching of nictating membrane, blanching of conjunctival tissue, ocular discharge-yellow and head tilt were noted in the test eye. Due to the severe irritation noted, the animal was euthanized following the 72 hour score.

Based on the initial rabbit dosed, the test item is considered to be a corrosive to the ocular tissue of the rabbit.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Eye irritation

The potential irritant and/or corrosive effects of the test item were evaluated on the eyes of New Zealand White rabbits. One rabbit received a 0.1000 g (0.1 mL weight equivalent) dose of the test item in the conjunctival sac of the right eye. The contralateral eye of the animal remained untreated and served as a control. The test and control eye was examined for signs of irritation for up to 72 hours following dosing. Due to the amount of irritation noted in the initial rabbit, the remaining animals were not dosed.

Exposure to the test article produced corneal opacity in the test eye at the 1 hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24 hour scoring interval. Iritis was observed in the test eye at the 1 hour scoring interval. Conjunctivitis (redness and swelling) was noted in the test eye at the 1 hour scoring interval. Additional ocular findings of blanching of nictating membrane, blanching of conjunctival tissue, ocular discharge-yellow and head tilt were noted in the test eye. Due to the severe irritation noted, the animal was euthanized following the 72 hour score.

Based on the initial rabbit dosed, the test item is considered to be a corrosive to the ocular tissue of the rabbit.

Skin corrosion

The potential irritant and/or corrosive effects of the test item were evaluated on the skin of New Zealand White rabbits in a study performed according to OECD 404, EC Regulation 124/92 method B.4 and EPA OPPTS 798.4470. Each of six rabbits received a 0.5 g dose of the test article as a single dermal application. The dose was held in contact with the skin under a semi-occlusive binder for an exposure period of four hours. Following the exposure period, the binder was removed and the remaining test article was wiped from the skin using gauze moistened with distilled water followed by dry gauze. Test sites were subsequently examined and scored for dermal irritation for up to 14 days following patch removal.

Exposure to the test article produced moderate edema and moderate to severe blanching on 6/6 test sites at the 1 hour scoring interval. Additional dermal findings included eschar exfoliation and desquamation which were noted on 4/6 and 5/6 test sites, respectively, and apparent necrosis and eschar which were both noted on 6/6 test sites. The dermal irritation resolved completely in 1/6 animals by study day 14.

Under the conditions of this test, the test item is considered to be a corrosive to the skin of the rabbit.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is classified as corrosive to skin Cat 1 (H314) and eye damaging Cat 1 (H318) under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.