Ethylenebis(oxyethylene) bis[3-(5-tert-butyl-4-hydroxy-m-tolyl)propionate]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28.8.1979 to 12.11.1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

light/dark cycle; flushing of 3 of the rabbits' eyes after exposure.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EPA 163.81-4 "Primary eye irritation study"

Deviations:

not specified

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethylenebis(oxyethylene) bis[3-(5-tert-butyl-4-hydroxy-m-tolyl)propionate]

EC Number:

253-039-2

EC Name:

Ethylenebis(oxyethylene) bis[3-(5-tert-butyl-4-hydroxy-m-tolyl)propionate]

Cas Number:

36443-68-2

Molecular formula:

C34H50O8

IUPAC Name:

ethane-1,2-diylbis(oxyethane-2,1-diyl) bis[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propanoate]

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Ciba-Geigy Limited
- Weight at study initiation: 2 to 3 kgs
- Housing: Individually in metal cages
- Diet: ad libitum standard rabbit food NAFAG No. 814
- Water: ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Photoperiod (hrs dark / hrs light): 14 hrs dark/ 10 hrs light

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 g

Duration of treatment / exposure:

In 3 of 6 rabbits the test substance was flushed with 10 mL of saline after 30 seconds of exposure, the other 3 rabbits did not have their eye flushed. The right eye of each rabbit served as the control.

Observation period (in vivo):

Observations were taken on day 1,2,3,4, and 7.

Number of animals or in vitro replicates:

6 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Flushing with 10 mL of saline in 3 of the rabbits' eyes
- Time after start of exposure: Washing occurred 30 seconds after exposure


SCORING SYSTEM:
Score for eye irritation in rabbits (Table 1)
CORNEA:
A Opacity and degree of density (most dense eurea scored)
No opacity = 0
Scattered or diffuse area, details of iris clearly visible = 1
Easily discernible translucent areas, details of iris slightly obscured = 2
Opalescent areas, no detiails of iris visible, size of pupil barely discernible = 3
Opaque, iris invisible = 4
B 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
Calculation of Score: A X B X 5
Maximum possible score = 80
IRIS
A Values
Normal = 0
Folds above normal, congestion, swelling, circumcornea 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
Calculation of score: A X 5
Maximum possible score « 10

CONJUNCTIVAE:
A Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal = 0
Vessels definitely injected cibove normal = 1
More diffuse, deeper crimson red, individual vessels not easily discernible = 2
Diffuse beefy red = 3
B Chemosis
No swelling = 0
Any swelling eibove normal (Includes nictitating membrane) = 1
Obvious swelling with partial eversion of lids = 2
Swelling with lids about half closed = 3
Swelling with lids about half closed to completely 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
Calculation of score: (A + B + C) X 2
Maximum possible score » 20

Calculation of the primary eye irritation index:
The mean reaction scores for cornea, iris and conjunctiva observed after 1, 2, 3, 4 and 7 days were summed up and the sum divided by 5. This procedure was carried out separately for unrinsed (A) and rinsed (B) eyes respectively.
Index
0 - 1 0 = Minimal
11 - 25 = Slight
26 - 55 = Moderate
56 - 84 = Marked
above 84 = Extreme
The ratio R = A : B indicates the effect of rinsing the eyes approximately 30 seconds after instillation of the compound.
If R is
<1 rinsing increased the effect of the compound
= 1 no effect
= 1.1 - 1.5 practically no effect
= 1.6 - 2 little but assessable effect
= 2.1 - 4 good effect
= 4.1 - 10 very good effect
>10 action of the compound practically abolished

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Score:

0

Max. score:

110

Remarks on result:

other: rinsed and unrinsed

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: rinsed and unrinsed

Results 3

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: rinsed and unrinsed

Results 4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

other: rinsed and unrinsed

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: rinsed and unrinsed

Irritant / corrosive response data:

No irritation

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS