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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04 August 2003 to 17 August 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed to GLP and in line with the standardised guidelines OECD 405, EU Method B.5 and EPA OPPTS 870.2400 with no deviations thought to impact the reliability of the presented results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
452-330-3
EC Name:
-
Cas Number:
314020-40-1
Molecular formula:
C14H20N2O2
IUPAC Name:
2-(2,6-diethyl-4-methyl-phenyl)propanediamide
Test material form:
solid: particulate/powder
Details on test material:
- Physical state: Powder, yellowish
- Storage condition of test material: In the dark at ambient temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Young adults
- Weight at study initiation: 2656-3148 g
- Housing: The animals were housed individually
- Diet: ad libitum
- Water: ad libitum, mains water
- Acclimation period: At least 5 days prior to study initiation

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 15 changes minimum
- Photoperiod (hrs dark / hrs light): 12 hours light (artificial), 12 hours dark

IN-LIFE DATES: From: 05 August 2003 To: 17 August 2003

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
- Dose administration: Approximately 100 mg of the test substance was applied into the conjunctival sac of the left eye of one rabbit by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped. The lids were then gently held together for 1-2 seconds after which the animal was released. The other eye was untreated (control eye).
Observation period (in vivo):
Animals were observed up to 7 days post administration
Number of animals or in vitro replicates:
One animal initially, followed by a further two animals once the irritation potential was fully assessed in the first animal.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Irrigation was not performed

SCORING SYSTEM:
The reactions observed were scored in accordance with the criteria of Draize (1959) and assessed using a modified form of the Kay and Calandra system (1962)

TOOL USED TO ASSESS SCORE: To aid scoring, animals were placed in an artificial daylight chamber for each assessment of irritation. In addition, as an aid in the assessment of corneal damage, fluorescing staining was used at all readings from 1 day after application.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Time point until effect occurred is given
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 1 hour
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 1 day
Remarks on result:
other: Time point until effect occurred is given
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 1 day
Remarks on result:
other: Time point until effect occurred is given
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 1 day
Remarks on result:
other: Time point until effect occurred is given
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 1 hour
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 1 day
Remarks on result:
other: Time point until effect occurred is given
Irritant / corrosive response data:
The maximum score for each parameter was calculated using the Draize (1959) scoring system as presented in table 1 under the field "Any other information on materials and methods incl. tables".

Application into the eye caused practically no initial pain (Class 1 on a 0-5 scale). There were no corneal iridial effects. Conjunctival effects consisted of slight redness in all animals up to 4 days and slight chemosis in two animals approximately 1 hour after application. In addition, one animal had slight erythema of the eyelids approximately 1 hour after application. All signs of irritation had completely resolved within 7 days of application.

Under the conditions of the study, the test material was considered to be mildly irritating to the unrinsed eye according to a modified form of the Kay and Calandra system.
Other effects:
There were no signs of ill-health in any animal during the study.

Any other information on results incl. tables

Table 3: Mean scores

Observation

1 h (3)*

1 d (3)

2 d (3)

3 d (3)

4 d (1)

7 d (1)

Cornea (Max 80)

0.0

0.0

0.0

0.0

0.0

0.0

Iris (Max 10)

0.0

0.0

0.0

0.0

0.0

0.0

Conjunctiva (Max 20)

3.3

0.7

0.7

0.7

2.0

0.0

Mean Total Score: (Max 110)

3.3

0.7

0.7

0.7

2.0

0.0

 *Numbers in parentheses indicate number of animals included in observation

Table 4: Individual scores

       Cornea        Iris     Conjunctiva           
 Animal number  Sex  Elapsed time  Opacity  Area  Score    Score  Redness  Chemosis  Discharge  Score  Total score
77   M  1 h  0  0  0  0  0  1  1  0  4  4
     1 d  0  0  0  0  0  1  0  0  2  2
     2 d  0  0  0  0  0  1  0  0  2  2
     3 d  0  0  0  0  0  1  0  0  2  2
     4 d  0  0  0  0  0  1  0  0  2  2
     7 d  0  0  0  0  0  0  0  0  0  0
 105  F  1.3 h  0  0  0  0  0  1  0  0  2  2
     1 d  0  0  0  0  0  0  0  0  0  0
     2 d  0  0  0  0  0  0  0  0  0  0
     3 d  0  0  0  0  0  0  0  0  0  0
 106 F  F  1.2 h  0  0  0  0  0  1  1  0  4  4
     1 d  0  0  0  0  0  0  0  0  0  0
     2 d  0  0  0  0  0  0  0  0  0  0
     3 d  0  0  0  0  0  0  0  0  0  0

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test material only elicited slight reactions in any of the animals during the course of the study that meant the test material does not require classification as an eye irritant. The study is considered to be reliable, relevant and adequate for risk assessment and classification and labelling purposes.
Executive summary:

The eye irritation of the test material was determined in accordance with the standardised guidelines OECD 405, EU Method B.5 and EPA OPPTS 870.2400. Approximately 100 mg of test material was applied into one one of each of three rabbits and were assessed for up to 7 days to determine the grade of ocular reaction. There were no iridial effects. Conjunctival effects consisted of slight redness in all animals for up to 4 days and slight chemosis in two animals approximately 1 hour after application. In addition, one animal had slight erythema of the eyelids approximately 1 hour after application. All signs of irritation had completely resolved within 7 days of application.

Under the conditions of the study, the test material was considered to be mildly irritating to the unrinsed eye according to modified form of the Kay and Calandra system. The test material does not require classification for eye irritation in line with Regulation No. 1272/2008.