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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:
2015-9-28 to 2015-11-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2016

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
Qualifier:
according to guideline
Guideline:
other: JMAFF Guidelines (2000), including the most recent revisions
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Methyl (1R,3S,4R,5R)-3-amino-5-({2,4,6-tri-O-benzoyl-3-O-[(2S)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl]-β-D-galactopyranosyl}oxy)-4-[(2,3,4-tri-O-benzyl-6-deoxy-α -L-galactopyranosyl)oxy]cyclohexanecarboxylate hydrochloride
EC Number:
945-311-0
Molecular formula:
C78H85NO18 HCl
IUPAC Name:
Methyl (1R,3S,4R,5R)-3-amino-5-({2,4,6-tri-O-benzoyl-3-O-[(2S)-1-(benzyloxy)-3-cyclohexyl-1-oxopropan-2-yl]-β-D-galactopyranosyl}oxy)-4-[(2,3,4-tri-O-benzyl-6-deoxy-α -L-galactopyranosyl)oxy]cyclohexanecarboxylate hydrochloride
Details on test material:
- State of aggregation: white solid powder
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: E010016142
- Expiration date of the lot/batch: 31 March 2016

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

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation: 12- 24 weeks
- Weight at study initiation: >=1.5 kg
- Housing: Cages with perforated floors and shelters
- Diet (e.g. ad libitum): 100 grams per day of a pelleted diet for rabbits
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >= 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%):40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 28.4 mg
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
72 hours
Duration of post- treatment incubation (in vitro):
No post-treatment incubation was conducted in vitro.
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 50 mL of tepid water
- Time after start of exposure: 1 hr

SCORING SYSTEM:
CORNEAL IRRITATION
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity (may include slight dulling of normal luster) 0
Scattered or diffuse areas of opacity, details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4
Area of cornea involved:
No ulceration or opacity 0
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
IRIS
Normal 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia,
or injection, any of these or combination thereof, iris still reacting to light
(sluggish reaction is positive) 1
No reaction to light, hemorrhage, gross destruction (any or all of these) 2
CONJUNCTIVAL IRRITATION
Redness (refers to palpebrae and sclera, excluding cornea and iris):
Blood vessels normal 0
Some blood vessels definitely hyperaemic (injected) 1
Diffuse, crimson color, individual vessels not easily discernible 2
Diffuse beefy red 3
Chemosis (refers to lids and/or nictitating membranes):
No swelling 0
Any swelling above normal (includes nictitating membranes) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4
Discharge:
No discharge (may include small amounts observed in inner canthus of normal animals) 0
Any amount different from normal and/or lacrimation 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge with moistening of the lids and hairs (considerable area around the eye) 3
Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an
ophthalmic examination lamp.

TOOL USED TO ASSESS SCORE: hand-slit lamp

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. 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. 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. 0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 60 min
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 60 min
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 60 min
Score:
ca. 0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 60 min
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 60 min
Score:
ca. 1
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 60 min
Score:
ca. 0
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 60 min
Score:
ca. 1
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 60 min
Score:
ca. 1
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 60 min
Score:
ca. 1
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24 h
Score:
ca. 1
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
48 h
Score:
ca. 0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
72 h
Score:
ca. 0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0.1
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
ca. 0
Irritant / corrosive response data:
There was no evidence of ocular corrosion.
Other effects:
Remnants of the test item were present in the eye of all animals on Day 1.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on these results, PF-06460259-01 does not have to be classified as an eye irritant according to GHS.