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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP; guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): trans-beta-farnesene
- CAS 18794-84-8

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source:Covance Research Products, Inc., Denver, PA
- Age at study initiation: 17 weeks
- Weight at study initiation: 2.7 - 2.9 kg
- Housing: individually housed in suspended stainless steel wire bottom cages. Paper bedding was placed beneath the cages and changed at least three times/week
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) was provided daily.
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.77 – 22.77 °C
- Humidity (%): 2.1 - 27%.
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

IN-LIFE DATES: From:1/6/09 To: 1/9/09

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral eye served as control
Amount / concentration applied:
0.1 ml in one eye
Duration of treatment / exposure:
Single dose
Observation period (in vivo):
The eyes were examined and scored by the Draize technique at 1, 24, 48 and 72 hours. Sodium fluorescein dye procedures were used at the 24-hour observation interval.
Number of animals or in vitro replicates:
3 (2 males; 1 female)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing

TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein

A Mini-Maglite® flashlight equipped with a high intensity bulb was used to aid in scoring.
Sodium fluorescein dye procedures were used at the 24-hour observation interval. The eye was
examined with the aid of an ultraviolet light source. Ocular reactions were graded according to the
numerical Draize technique.

SCORING SYSTEM:
SCORING SYSTEM: Ocular reactions were graded according to the numerical Draize technique, summarized below.

SCALE FOR SCORING OCULAR LESIONS (Draize, J. H. et al. J. Pharm. Exp. Ther. 82:377-390, 1944).
(1) CORNEA:
(A) Opacity: Degree of density (area most dense taken for reading):
No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster),details of iris clearly visible 1(*)
Easily discernible translucent area, details of iris slightly obscured 2(*)
Opalescent areas, no details of iris visible, size of pupil barely discernible 3(*)
Opaque cornea, iris not discernible through the opacity 4(*)
(B) Area of cornea Involved:
One quarter (or less) but not zero 1
Greater than one-quarter, but less than one-half 2
Greater than one-half, but less than three-quarters 3
Greater than three quarters up to whole area 4
SCORE EQUALS A x B x 5 Maximum Total 80

(2) IRIS:
(A) 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, hemorrhage, gross destruction (any or all of these) 2(*)
SCORE EQUALS A x 5 Maximum Total 10

(3) CONJUNCTIVAE:
(A) REDNESS (refers to palpebral and bulbar conjunctivae excluding cornea & iris):
Blood vessels normal 0
Some blood vessels definitely hyperemic (injected) 1
More diffuse, deeper crimson red, individual vessels not easily discernible 2(*)
Diffuse beefy red 3(*)
(B) CHEMOSIS
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(*)
(C) 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 and considerable area around the eye 3
SCORE EQUALS (A+B+C)x2 Maximum Total 20

The maximum total score is the sum of all scores obtained for the cornea, iris and conjunctivae.
4.
(*)Indicates a positive response

ULTRAVIOLET FLUORESCEIN SCAN SCORING CODE:

0 = Negative
1 = Positive with an area 1/4 or less
2 = Positive with an area >1/4 but <1/2
3 = Positive with an area >1/2, but <3/4
4 = Positive with an area >3/4, up to entire area

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable; no opacity
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
Ocular Findings, Systemic Observations and Body Weights

An.#/Sex Item Tissue Reading Hour 1 Hour 24 Hour 48 Hour 72
H2116/M A Cornea Opacity 0 0 0 0
B Area 0 0 0 0
1. Total=(AxB)x5 0 0 0 0
C Iris 0 0 0 0
2. Total=Cx5 0 0 0 0
D Conjunctiva Redness 2 1 0 0
E Chemosis 1 0 0 0
F Discharge 0 0 0 0
3. Total=(D+E+F)x2 6 2 0 0

Total=1+2+3 6 2 0 0

Systemic Observations A A A A
Sodium Fluorescein 0 N/A N/A
Pretest Body Weight - 2.9 kg


An.#/Sex Item Tissue Reading Hour 1 Hour 24 Hour 48 Hour 72
H2120/M A Cornea Opacity 0 0 0 0
B Area 0 0 0 0
1. Total=(AxB)x5 0 0 0 0
C Iris 0 0 0 0
2. Total=Cx5 0 0 0 0
D Conjunctiva Redness 2 1 1 0
E Chemosis 1 0 0 0
F Discharge 1 0 0 0
3. Total=(D+E+F)x2 8 2 2 0
Total=1+2+3 8 2 2 0

Systemic Observations A A A A
Sodium Fluorescein 0 N/A N/A
Pretest Body Weight - 2.7 kg

An.#/Sex Item Tissue Reading Hour 1 Hour 24 Hour 48 Hour 72
H2148/F A Cornea Opacity 0 0 0 0
B Area 0 0 0 0
1. Total=(AxB)x5 0 0 0 0
C Iris 0 0 0 0
2. Total=Cx5 0 0 0 0
D Conjunctiva Redness 2 1 0 0
E Chemosis 1 0 0 0
F Discharge 1 0 0 0
3. Total=(D+E+F)x2 8 2 0 0
Total=1+2+3 8 2 0 0
Systemic Observations A A A A
Sodium Fluorescein 0 N/A N/A
Pretest Body Weight - 2.8 kg

A = Normal N/A = not applicable

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Farnesene is not classifiable as an eye irritant per EU CLP criteria.
Executive summary:

Three healthy New Zealand White rabbits (2 males - 1 female), free from evidence of

ocular irritation and corneal abnormalities, were dosed with trans-ß-farnesene, Lot# KJF-134-53-03,

CAS# 18794-84-8. The test article (0.1 ml) was placed into the conjunctival sac of one eye of each

rabbit. The contralateral eye served as a control. The eyes were examined and scored by the Draize

technique at 1, 24, 48 and 72 hours. Sodium fluorescein dye procedures were used at the 24-hour

observation interval. Body weights were recorded pretest.

There was no corneal opacity or iritis noted in any animal at any observation period. Mild conjunctival irritation (redness, swelling and some discharge) noted in the eyes of 3/3 animals 1 hr after treatment had cleared within 72 hours. There were no abnormal physical signs noted during the observation period.

Following instillation into the rabbit eye, trans-beta farnesene provoked only minimal occular irritation. Reactions did not meet the criteria for classification as an eye irritant per EU CLP criteria.