2-oxocyclohexane-1,1,3,3-tetrapropionic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Start of experiment: June 26, 1990 ; End of experiment: July 3, 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-oxocyclohexane-1,1,3,3-tetrapropionic acid

EC Number:

225-833-9

EC Name:

2-oxocyclohexane-1,1,3,3-tetrapropionic acid

Cas Number:

5107-67-5

Molecular formula:

C18H26O9

IUPAC Name:

3-[1,3,3-tris(2-carboxyethyl)-2-oxocyclohexyl]propanoic acid

Test material form:

not specified

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The albino rabbit is the recommended species for Acute Eye Irritation/Corrosion studies.
- Animal strain: New Zealand white rabbits (Chbb:NZW)
- Breeder: Dr. K. Thomae, GMBH Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Acclimatisation period: at least 5 days

The test was performed on 3 female rabbits, checked for normaleye conditions, weighing between 2320 to 2600 g (approx. 9-13 weeks old) .
The animals were housed individually in metal cages, identified by ear tattoo, kept at a constant room temperature of 20+/- 3 °C, at a relative humidity of 30-70 % and on a 12 hours light cycle day.

The rabbits received ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland - and fresh water. All batches of the diet are assayed for nutritive ingredients and contaminant level by the manufacturer. Analytical results are available at the animal supply office.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye of each animal remained untreated and served as a control.

Amount / concentration applied:

0.1 ml (47 mg)

Duration of treatment / exposure:

one single application in the conjunctival sac of the left eye of each animal.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 female rabbits

Details on study design:

0.1 ml (47 mg) of TK 1333 2 was placed into the conjunctival sac of the left eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second in order to prevent loss of the test article.
The right eye remained untreated and served as a control.
The ocular reactions were evaluated 1, 24, 48, and 72 hours after the instillation of TK 13332 according to the OECD scoring system.
A slit-lamp was used to facilitate the evaluation.

SCORING SYSTEM:

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 lustre), details of iris clearly visible: 1
- Easily discernible translucent area, details of iris slightly obscured: 2
- Nacrous area, no details of iris visible, size of pupil barely discernible: 3
- Opaque cornea, iris not discernible through the opacity: 4

IRIS
- Normal: 0
- Markedly deepended rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive): 1
- No reaction to light, haemorrhage, gross destruction ( any or all of these ): 2

CONJUNCTIVAE
Redness : (refers to palpebral and bulbar conjunctivae, cornea and iris)
- Blood vessels normal: 0
- Some blood vessels definitely hyperaemic (injected): 1
- Diffuse, crimson colour, individual vessels not easily discernible: 2
- Diffusy beefy red: 3

Chemosis: lids and/or nictating membranes
- No swelling: 0
- Any swelling above normal (includes nictating 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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

0.33

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Max score observed is 1 and this until 24 hours after application.

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

0.33

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Max score observed is 1 and this until 24 hours after application.

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

0

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Max score observed is 1 and this until 1 hour after application.

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

0

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Max score observed is 1 and this during the first hour after application.

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

0

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

0

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Max score observed is 1 and this during the first hour after application.

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Max score observed is 2 and this until 24 hours after application and then 1 until 48 hours after application.

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

1

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Max score observed is 2 and this until 24 hours after application and then 1 until 48 hours after application.

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

1.67

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Max score observed is 2 and this until 48 hours after application and then 1 until 72 hours after application.

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

0.67

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Max score observed is 2 and this 1 hour after application and then 1 until 48 hours after application.

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

0.67

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Max score observed is 2 and this 1 hour after application and then 1 until 48 hours after application.

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean

Time point:

other: mean 24-72 hours

Score:

0.67

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Max score observed is 2 and this 24 hours after application and then 1 until 48 hours after application.

Irritant / corrosive response data:

Because reactions were observed within 72 hours after instillation of the test article, the observation period was extended to 7 days to determine the reversibility of the eye reactions.

Any other information on results incl. tables

Individual eye scores.

	CORNEA	IRIS	CONJUNCTIVA
Animal N° 834/F	ce/te	ce/te	ce/te	ce/te
After 1 hr	0/1	0/1	0/2	0/2
After 24 hrs	0/1	0/0	0/2	0/1
After 48 hrs	0/0	0/0	0/1	0/1
After 72 hrs	0/0	0/0	0/0	0/0
Mean (24 - 72 hrs)	0/0.33	0/0	0/1	0/0.67
After 7 days	0/0	0/0	0/0	0/0

	CORNEA	IRIS	CONJUNCTIVA
Animal N° 888/F	ce/te	ce/te	ce/te	ce/te
After 1 hr	0/1	0/0	0/2	0/2
After 24 hrs	0/1	0/0	0/2	0/1
After 48 hrs	0/0	0/0	0/1	0/1
After 72 hrs	0/0	0/0	0/0	0/0
Mean (24 - 72 hrs)	0/0.33	0/0	0/1	0/0.67
After 7 days	0/0	0/0	0/0	0/0

	CORNEA	IRIS	CONJUNCTIVA
Animal N° 116/F	ce/te	ce/te	ce/te	ce/te
After 1 hr	0/1	0/1	0/2	0/2
After 24 hrs	0/0	0/0	0/2	0/2
After 48 hrs	0/0	0/0	0/2	0/1
After 72 hrs	0/0	0/0	0/1	0/0
Mean (24 - 72 hrs)	0/0	0/0	0/1.67	0/1
After 7 days	0/0	0/0	0/0	0/0

ce = control eye

te = test eye

M = Male

F = Female

Body weight (g)

Animal N°	834/F	888/F	116/F
At start of test	2430	2600	2320
After 3 days	2460	2680	2330
After 7 days (end)	2560	2800	2460

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Regarding the results obtained 24 to 72 hours after instillation, the test item can be classified as non-irritant to albino rabbit's eye.
The eye reactions observed were reversible until the end of the observation period on day 7.

Executive summary:

The acute eye irritation/corrosion in albino rabbits was performed to determine the irritant or corrosive potency of the test item in the albino rabbit eye and the associated mucous membranes.

This test was based on the OECD Guideline N° 405, adopted in May 12, 1981.

Under the experimental conditions employed, the test item, induced irritation of the cornea, iris , and conjunctiva when instilled into the

conjunctival sac of female albino rabbits.

Because the mean values of the readings 24 t o 72 hours after instillation are below the threshold of significance, the test item can be classified as non-irritant.