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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:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Farnesane
- CAS number: 3891-98-3

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 on 07/07/10 & 08/04/10
- Age at study initiation: The animals were born on 03/13/10 & 04/17/10. Study Initiation on 08/24/10
- Weight at study initiation: The pretest body weight range was 2.4 - 3.2 kg.
- Housing: The animals were identified by cage notation and a uniquely numbered metal eartag. The animals were housed 1/cage in suspended 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: Minimum of 5 days

ENVIRONMENTAL CONDITIONS: The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12-hour light/dark cycle, and was kept clean and vermin free.

IN-LIFE DATES: From: 8/24/10 To: 8/27/10

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Contralateral, untreated eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): neat


Duration of treatment / exposure:
The test article (0.1 ml) was placed by syringe into the conjunctival sac that was formed by gently pulling the lower eyelid away from the eye. After instillation, the lids were held together for approximately one second to insure adequate distribution of the test article. One eye of each rabbit was dosed. The contralateral eye served as a control.

Observation period (in vivo):
Type and Frequency of Observations
The treated and control eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours. 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 in the treated eyes. The eyes were examined with the aid of an ultraviolet light source. Ocular reactions were graded according to the numerical Draize technique.

Body weights were recorded pretest.

Observations for mortality, toxicity and pharmacological effects were recorded at each ocular observation period. All animals were humanely sacrificed using CO2 following study termination.
Number of animals or in vitro replicates:
Three rabbits (males), free from evidence of ocular irritation or abnormalities, were assigned to this study without conscious bias. Prior to being selected for this study, both eyes of each animal were examined for any evidence of irritation or abnormalities of the cornea, iris and/or conjunctiva. A Mini-Maglite® flashlight equipped with a high intensity bulb was used to aid in the examination. Only animals in apparent good health were made available for study assignment.
Details on study design:
REMOVAL OF TEST SUBSTANCE: No removal
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




TOOL USED TO ASSESS SCORE: To screen for any evidence of irritation or abnormalities of the cornea, iris and/or conjunctiva prior to start of test, A Mini-Maglite® flashlight equipped with a high intensity bulb was used to aid in scoring. The treated and control eye of each rabbit was examined for irritation of the cornea, iris and conjunctiva at 1, 24, 48 and 72 hours. 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 in the treated eyes. The eyes were examined with the aid of an ultraviolet light source. Ocular reactions were graded according to the numerical Draize technique.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: Mean of animals 1, 2, & 3
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: Mean of animals 1, 2, & 3
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: Mean of animals 1, 2, & 3
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal: Mean of animals 1, 2, & 3
Time point:
24/48/72 h
Score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1, 24, 48, and 72 hours
Score:
0
Remarks on result:
other: See "any other information on results incl. tables" for complete data summary
Irritant / corrosive response data:
There was no corneal opacity, iritis or conjunctival irritation noted at any observation period.
The control eyes appeared normal at all observation periods.
Systemic Observations: There were no abnormal physical signs noted during the observation period.

Other effects:
None observed

Any other information on results incl. tables

Ocular Findings, Systemic Observations, and Body Weights

Animal/Sex

Item

Tissue

Reading

1 hour

24 hour

48 hour

72 hour

H3492/M

A

Cornea

Opacity

0

0

0

0

 

B

Area

0

0

0

0

 

1.      

0

0

0

0

 

C

Iris

 

0

0

0

0

 

2.       = (C x 5)

 

0

0

0

0

 

D

Conjunctiva

Redness

0

0

0

0

 

E

 

Chemosis

0

0

0

0

 

F

 

Discharge

0

0

0

0

 

3.      

 

0

0

0

0

 

      Total 1 + 2+ 3

 

0

0

0

0

 

Systemic Observations

 

A

A

A

A

 

Sodium Fluorescein

 

 

0

NA

NA

 

Pretest Body Weight : 3.2 Kg

 

 

 

 

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Animal/Sex

Item

Tissue

Reading

1 hour

24 hour

48 hour

72 hour

H3555/M

A

Cornea

Opacity

0

0

0

0

 

B

 

Area

0

0

0

0

 

1.      

0

0

0

0

 

C

Iris

 

0

0

0

0

 

2.       = (C x 5)

 

0

0

0

0

 

D

Conjunctiva

Redness

0

0

0

0

 

E

 

Chemosis

0

0

0

0

 

F

 

Discharge

0

0

0

0

 

3.      

0

0

0

0

 

 

      Total 1 + 2+ 3

 

0

0

0

0

 

Systemic Observations

 

A

A

A

A

 

Sodium Fluorescein

 

 

0

NA

NA

 

Pretest Body Weight : 2.4 Kg

 

 

 

 

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Animal/Sex

Item

Tissue

Reading

1 hour

24 hour

48 hour

72 hour

H3539/M

A

Cornea

Opacity

0

0

0

0

 

B

 

Area

0

0

0

0

 

1.      

 

0

0

 

 

 

C

Iris

 

0

0

0

0

 

2.       = (C x 5)

 

0

0

0

0

 

D

Conjunctiva

Redness

0

0

0

0

 

E

 

Chemosis

0

0

0

0

 

F

 

Discharge

0

0

0

0

 

3.      

 

0

0

0

0

 

      Total 1 + 2+ 3

 

0

0

0

0

 

Systemic Observations

 

A

A

A

A

 

Sodium Fluorescein

 

 

0

NA

NA

 

Pretest Body Weight : 2.5 Kg

 

 

 

 

A = Normal; NA = Not applicable

Applicant's summary and conclusion

Interpretation of results:
other: Not irritating
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Ocular administration of Farnesane CAS# 3891-98-3 did not produce irritation.
Executive summary:

Objective: To determine the irritant and/or corrosive effects, if any, of a test article when instilled into the rabbit eye. This study was designed to comply with the standards set forth in EPA Health Effects Testing Guidelines, OPPTS Series 870.2400, final guideline, August 1998.

 

Method Synopsis: Three healthy New Zealand White rabbits (males), free from evidence of ocular irritation and corneal abnormalities, were dosed with Farnesane CAS# 3891-98-3.  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. The control eyes were examined at the same time periods. Sodium fluorescein dye procedures were used at the 24-hour observation interval. Observations for mortality, toxicity and pharmacological effects were recorded at each ocular observation period. Body weights were recorded pretest.

 

Summary: 

 

There was no corneal opacity, iritis or conjunctival irritation noted at any observation period.

 

The control eyes appeared normal at all observation periods.

 

There were no abnormal physical signs noted during the observation period.

 

Conclusion: Ocular administration of Farnesane CAS# 3891-98-3 did not produce irritation.