Registration Dossier

Administrative data

Description of key information

Studies of skin irritation in the rabbit identified corrosivity and severe eye irritaion.  The results of an acute inhalation toxicity study indicate that mortality is associated with local irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

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:
weight of evidence
Study period:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study appears to follow to OECD guideline 405. However it is not GLP (GLP was not mandatory when study was done). There is no information on the purity of test, the source and age of the animals, on housing and environmental conditions. However, it is considered that the study still provides scientific and valid information.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
There is no information on the purity of test, the source and age of the animals, on housing and environmental conditions. However, it is considered that the study still provides scientific and valid information.
GLP compliance:
no
Remarks:
not mandatory when the study was carried out
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No information available in the test report
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.005 mL
Duration of treatment / exposure:
The eyelids were held together for one second following instillation to prevent immediate removal of test material. The eyes were not subsequently rinsed or flushed with water, saline or fluorescein.
Observation period (in vivo):
Up to 21 days. Eye effects were recorded at 1 hour, 4, 24, 48 and 72 hours, 7, 14 and 21 days
Number of animals or in vitro replicates:
6 animals (3 males and 3 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): None reported
- Time after start of exposure:

SCORING SYSTEM: Similar to the scale described in OECD guideline 405.

TOOL USED TO ASSESS SCORE: fluorescein (2%) staining was used to determine corneal injury before dosing and at readings after one day.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hours
Score:
3.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
3.7
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
Severe corneal opacity and conjunctival redness and chemosis were reported in all animals. All 6/6 animals at 24 and 48 hours and 4/6 animals at 72 hours displayed opalescent areas, iris details not visible and pupil size barely discernible. Two animals showed corneal opacity at the 72 hour timepoint. On day 7, 4/6 animals showed corneal opacity. By the end of the study all animals were affected. Damage to the cornea did not allow for the examination the iris of each eye.
Diffuse beefy red eyes were seen in all animals throughout the study. Most animals had swelling with lids about half closed to completely closed up to 72 hours after exposure. On day 7, chemosis decreased in one animals but 5/6 animals still showed swelling with lids about half closed to completely closed. On day 14, swelling with lids about half closed remained in 3/6 animals and a decrease in conjunctival chemosis was observed in 3 animals. However at the end of the study swelling with lids about half closed was reported in most animals.
The test substance is highly corrosive and the effects reported 1 hour after exposure persisted until the end of the study. Only chemosis was slightly reduced at the end of the study.
Other effects:
Immediate discomfort was reported by excessive blinking and pawing at eyes. Necrosis on conjunctivae and nictitating membrane along with red brown discharge were noted. At 3 days one rabbit developed a corneal bulge, Corneal bulge abd corneal vascularisation was noted in several animals between day 2 and 14. An opaque white surface on the cornea was also apparent in a few animals.

Table 1: Cornea and Iris irritation scores

 

Cornea opacity

Iris

Animal

83-22784

83-22783

83-22782

83-22815

83-22816

83-22820

83-22784

83-22783

83-22782

83-22815

83-22816

83-22820

Readings

 

 

 

 

 

 

 

 

 

 

 

 

1 hour

2

3

3

3

3

2

*

*

*

*

*

*

4 hours

2

3

3

3

3

2

*

*

*

*

*

*

24 hours

3

3

3

3

3

3

*

*

*

*

*

*

48 hours

3

3

3

3

3

3

*

*

*

*

*

*

72 hours

3

3

4

3

3

4

*

*

*

*

*

*

7 days

4

4

4

3

3

4

*

*

*

*

*

*

14 days

4

4

4

4

4

4

*

*

*

*

*

*

21 days

4

4

4

4

4

4

*

*

*

*

*

*

Mean per animal (24-72 hours)

3

3

3.3

3

3

3.3

*

*

*

*

*

*

Mean

(24-72 hours)

3.1

*

*Scoring not possible due to cornea opacity

Table 2: Conjunctival redness and chemosis scores

 

Conjunctival redness

Chemosis

Animal

83-22784

83-22783

83-22782

83-22815

83-22816

83-22820

83-22784

83-22783

83-22782

83-22815

83-22816

83-22820

Readings

 

 

 

 

 

 

 

 

 

 

 

 

1 hour

3

3

3

3

3

3

3

4

4

3

4

4

4 hour

3

3

3

3

3

3

4

4

4

3

4

4

24 hours

3

3

3

3

3

3

3

4

4

4

3

4

48 hours

3

3

3

3

3

3

4

4

4

4

3

4

72 hours

3

3

3

3

3

3

4

4

4

4

3

4

7 days

3

3

3

3

3

3

4

4

2

3

3

3

14 days

3

3

2

2

2

3

3

3

2

2

2

3

21 days

3

3

2

2

2

3

3

3

3

2

3

3

Mean per animal (24-72 hours)

3

3

3

3

3

3

3.7

4

4

4

3

4

Mean

(24-72 hours)

3

3.8

 

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance was shown to cause seious eye damage under the conditions of this study.
Executive summary:

 The test substance NIAX® Catalyst C·210 (0.005 mL) was instilled into the conjunctival sac of one eye of each animal (three males and three females New Zealand White rabbits). The eyelids was held together for one second. The eyes were examined and scored at one hour, 4, 24, 48 and 72 hours, 7, 14 and 21 days. Fluorescein was used to determine corneal injury before dosing and at readings after 24 hours.

Corneal opacity and conjunctival injury was reported in all animals and persisted through the study. Due to corneal opacity, the iris could not be examined. Necrosis of conjunctivae and nictitating membrane were observed. Corneal bulge and corneal vascularisation was apparent in several animals between day 2 and 14.

Under the conditions of this study, NIAX® Catalyst C·210 is classified as serious damage eye damage 1 ( substance according to Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

The substance is shown to be corrosive to skin and a severe eye irritant; classification as Corrosive is proposed, according to CLP criteria.


Justification for selection of skin irritation / corrosion endpoint:
Guideline-compliant studies are available: a weight of evidence approach is taken for this endpoint.

Justification for selection of eye irritation endpoint:
Only one study is available for this endpoint.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Based on the available data, the substance is classified according to the CLP Regulation (Reulation 1272/2008) as Corrosive (Category 1A) with the hazard statement H314: Causes severe skin burns and eye damage