Reaction mass of 1,3-diacetoxypropan-2-yl 12-acetoxyoctadecanoate and 2,3-diacetoxypropyl 12-acetoxyoctadecanoate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 2003-09-23 and 2003-11-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline and GLP study with no deviations.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

NA

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

451-530-8

EC Name:

-

Cas Number:

736150-63-3

Molecular formula:

Not applicable

IUPAC Name:

1,3-bis(acetyloxy)propan-2-yl 12-(carboxyoxy)octadecanoate; 2,3-bis(acetyloxy)propyl 12-(acetyloxy)octadecanoate

Details on test material:

Name of test material (as cited in study report): TS-ED 532
- Lot/batch No.: batch 10102
- Expiration date of the lot/batch: 2003-11-23

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: rabbit
- Age at study initiation: 13-14 weeks (male) and 11-12 weeks (female)
- Weight at study initiation: 2305 g (male), 2167 g and 2398 g (both female)
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 changes per h
- 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): 0.1 mL into the left eye of each of the rabbits.
- Concentration (if solution): undiluted

Duration of treatment / exposure:

72 h

Observation period (in vivo):

The scoring of eye irritation effects was performed at 1, 24, 48 and 72 h after installation of TS-ED 532. Observations of viability/mortality and clinical signs were performed daily from acclimatization to termination. The bodyweights were measured at start of acclimatization, on the days of application and at termination.

Number of animals or in vitro replicates:

3 (1 male and 2 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing after installation

SCORING SYSTEM:
The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commision Directive 92/69/EEC, July 31, 1992 approximately 1, 24, 48, 72 h after installation.

Grading of Ocular Lesions
CORNEA
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
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
Zero: 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 hyperemia, or injection, any 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

CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae when compared with control eye)
Blood vessels normal: 0
Some blood vessels definitely hyperemic (injected): 1
Diffuse, crimson color, individual vessels not easily discernible: 2
Diffuse beefy red: 3
Chemosis: lids and/or nictitating membranes
No swelling: 0
Any swelling above normal (including 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: 0
Any amount different to normal (does not include small amount observed in inner canthus of normal animal): 1
Discharge with moistening of the lids and hairs just adjacent to the lids: 2
Discharge with moistening of the lids and hairs, and a considerable area around the eye (running): 3

Note: Reddening of the sclerae will be assessed using the same scoring grades as conjunctivae.


TOOL USED TO ASSESS SCORE: diagnostic-lamp and fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

mean score 1

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

mean score 2

Time point:

other: overall at 24, 48 and 72 h

Score:

0.33

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

mean score 3

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 4

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Max. score:

1

Remarks on result:

other: Max. duration: 24 h; Max. value at end of observation period: 0 (related to all animals)

Results 5

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean score 1

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 6

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean score 2

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 7

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean score 3

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 8

Irritation parameter:

chemosis score

Max. score:

0

Remarks on result:

other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean score 1

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 10

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean score 2

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 11

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean score 3

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 12

Irritation parameter:

cornea opacity score

Max. score:

0

Remarks on result:

other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)

Results 13

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean score 1

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 14

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean score 2

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 15

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean score 3

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 16

Irritation parameter:

iris score

Max. score:

0

Remarks on result:

other: Max. duration: h; Max. value at end of observation period: 0 (related to all animals)

Irritant / corrosive response data:

The instillation of TS-ED 532 into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. The observed effect were fully reversible within 2 days.

Overall assessment of eye irritation scores for corneal opacity and iris: Not irritating

Overall assessment of eye irritation scores for conjunctivae( redness and chemosis): Not irritating


The individual scores for eye irritation are described in Table 1.

Other effects:

No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes was observed and no clinical signs were observed.

Any other information on results incl. tables

Table 1 Eye irritation scores – individual scores

Animal Number	Sex	Evaluation interval	Corneal Opacity	Iris	Conjunctivae Redness	Conjunctivae Chemosis	Sclera
94 95 96	M F F	1 hour	0 0 0	0 0 0	1 1 1	0 1 0	0 1 1
94 95 96	M F F	24 hours	0 0 0	0 0 0	1 1 0	0 0 0	0 0 0
94 95 96	M F F	48 hours	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
94 95 96	M F F	72 hours	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The primary eye irritation potential of TS-ED 532 was tested in 3 rabbits. Based on the results, it is concluded that TS-ED 532 is not irritating.

Executive summary:

The primary eye irritation potential of TS-ED 532 was tested in 3 rabbits by instilation of 0.1 mL TS-ED 532 into the left eye of each rabbit. The right eye served as control. The duration of treatment was 72 h. The scoring of irritation effects was performed 1, 24, 48 and 72 h after instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 h after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately.

The individual mean scores for corneal opacity and iris were 0.00 for all 3 rabbits. The individual mean scores for conjunctivae were 0.33, 0.33 and 0.00 for reddening, and 0.00 for chemosis in all 3 rabbits.

The instillation of TS-ED 532 into the eyes resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and chemosis. These effects were reversible and no longer evident 48 h after treatment. No abnormal findings were observed in the cornea or iris. TS-ED 532 caused no staining of the treated eyes and no corrosive effects were observed. No clinical signs of TS-ED 532 related effects were observed.

Overall, TS-ED 532 did not induce significant or irreversible damage to the rabbit eye. Hence, TS-ED 532 is considered to be not irritating to rabbit eye.