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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:
2008-04-28 to 2008-05-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

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
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
(R)-2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenol
EC Number:
929-946-0
Cas Number:
286930-02-7
Molecular formula:
C22 H31 N O2
IUPAC Name:
(R)-2-(3-(diisopropylamino)-1-phenylpropyl)-4-(hydroxymethyl)phenol
Test material form:
solid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor and 902/695838/D/2/1

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: twelve to twenty weeks
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: suspended cages
- Diet (e.g. ad libitum): Certified rabit diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
1 second
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM:
1. CONJUNCTIVAE
Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal 0
Vessels definitely injected above normal 1
More diffuse, deeper crimson red, individual vessels not easily discernible 2
Diffuse beefy red 3

Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids half closed to completely closed 4

Discharge
No discharge 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs a considerable area around the eye 3

2. IRIS
Normal 0
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2

3. CORNEA
Degree of Opacity (most dense area used)
No opacity 0
Scattered or diffuse areas, details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Opalescent areas, no details of iris visible, size of pupil barely discernible 3
Opaque, iris not discernible through the opacity 4

Area of Cornea Involved
One quarter (or less) but not zero 1
Greater than one quarter but less than half 2
Greater than half but less than three quarters 3
Greater than three quarters, up to whole area 4
TOTAL SCORE = (E x F) x 5
MAXIMUM TOTAL = 80

TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 60 min
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
7 d
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
14 d
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 60 min
Score:
ca. 1
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Irritation parameter:
iris score
Basis:
animal #2
Time point:
7 d
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
14 d
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 60 min
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 1
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
7 d
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
14 d
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 60 min
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
7 d
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
14 d
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 60 min
Score:
ca. 1
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 1
Irritation parameter:
iris score
Basis:
animal #1
Time point:
7 d
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
14 d
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 60 min
Score:
ca. 1
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 1
Irritation parameter:
iris score
Basis:
animal #3
Time point:
7 d
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
14 d
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 60 min
Score:
ca. 2
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48 h
Score:
ca. 2
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
72 h
Score:
ca. 1
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
7 d
Score:
ca. 1
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
14 d
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 60 min
Score:
ca. 3
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48 h
Score:
ca. 2
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
ca. 1
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
7 d
Score:
ca. 1
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
14 d
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 60 min
Score:
ca. 3
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48 h
Score:
ca. 2
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
72 h
Score:
ca. 1
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
7 d
Score:
ca. 1
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
14 d
Score:
ca. 0
Irritant / corrosive response data:
Scattered or diffuse corneal opacity was noted in all treated eyes at the 24, 48 and 72-hour observations.
Iridial inflammation was noted in all treated eyes one hour after treatment and at the 24, 48 and 72-hour observations.
Severe conjunctival irritation was noted in two treated eyes with moderate conjunctival irritation noted in the remaining treated eye one hour after treatment. Moderate conjunctival irritation was noted in all treated eyes at the 24, 48 and 72-hour observations with minimal conjunctival irritation noted at the 7-day observation.
Other effects:
- Lesions and clinical observations: Petechial haemorrhage of the nictitating membrane was noted in all treated eyes at the 24, 48 and 72-hour observations and in two treated eyes at the 7-day observation.
- Ophthalmoscopic findings: Dilation of the pupil, in comparison to the control eye, was noted in two test eyes one hour after treatment and at the 24-hour observation and in all test eyes at the 48-hour observation. The reaction had reversed in all treated eyes by the 72-hour observation.
All treated eyes appeared normal at the 14-day observation.

Applicant's summary and conclusion

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
The test material was classified in category 2A according to the GHS criteria.