1-O-β-(2 ,3-di-O-alka(e)noyl-6 -O-acetyl-D-mannopyranosyl)-D-erythritol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07th February - 05th April 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Deviations:

not specified

Remarks:

However, the temperature and humidity ranges are outside Guideline specifications.

GLP compliance:

no

Remarks:

The experiment was performed in 2007, therefore pre-dating 1st June 2008 cut off after which GLP compliance is necessary for toxicological tests. The report is dated 2019, because this is when the report itself was finalised.

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

126482-45-2

Test material form:

liquid

Details on test material:

Storage of test material: in a tightly sealed container, under refrigeration
Informal name: MEL-2

Test animals / tissue source

Species:

rabbit

Strain:

other: Kbl:NZW[SPF]

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated one eye

Amount / concentration applied:

0.1ml

Duration of treatment / exposure:

One second

Observation period (in vivo):

1, 24, 48 and 72 hours

Duration of post- treatment incubation (in vitro):

n/a

Number of animals or in vitro replicates:

3

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

animal: Mean score

Time point:

24 h

Score:

8.8

Max. score:

110

Reversibility:

other: Irritant

Remarks on result:

probability of mild irritation

Results 2

Irritation parameter:

overall irritation score

Basis:

animal: Mean Score

Time point:

48 h

Score:

4

Max. score:

110

Reversibility:

other: Irritant

Remarks on result:

probability of mild irritation

Results 3

Irritation parameter:

overall irritation score

Basis:

animal: Mean score

Time point:

72 h

Score:

3.4

Max. score:

110

Reversibility:

other: irriatnt

Remarks on result:

probability of mild irritation

Results 4

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

24 h

Score:

8

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Results 5

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

48 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Results 6

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

72 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Results 7

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

24 h

Score:

10

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Results 8

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

48 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Results 9

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

72 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Results 10

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

24 h

Score:

8

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Results 11

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

48 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Results 12

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

72 h

Score:

2

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of weak irritation

Results 13

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 14

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 15

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 16

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 17

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 18

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 19

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 20

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 21

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 22

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 23

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 24

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 25

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 26

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 27

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 28

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: 48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 29

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Results 30

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test item was not corrosive but it was considered to be ‘Minimally irritating’ to rabbit eyes under the conditions of this study.

Any other information on results incl. tables

Table 2. Mean scores ocular irritation in rabbits

No. of animal: 3
Ocular Reactions	Categories of response	Time after application
Conjunctivae		1h	24h	48h	72h
	A.Redness	1.0	1.7	1.0	1.0
	B. Chemosis	2.3	2.0	1.0	0.7
	C. Discharge	2.0	0.7	0	0
	Weighted score: (A+B+C) x 2 = Total maximum score of 20	10.6	8.8	4	3.4
Cornea	A.Opacity-degree of density	0	0	0	0
	B. Area of cornea invloved	0	0	0	0
	Weighted score: (AxBx5) = Total maximum score of 80	0	0	0	0
Iris	A	0	0	0	0
	Weighted scores: Ax5 = Total maximum =10	0	0	0	0
Total possible maximum = Sum of total maximum scores		10.6	8.8	4	3.4

Table 3. Individual ocular irritation in rabbits

Time after application
Ocular Reactions	Categories of response	Animal #1				Animal #2				Animal #3
Conjunctivae		1h	24h	48h	72h	1h	24h	48h	72h	1h	24h	48h	72h
	A.Redness	1	1	1	1	1	2	1	1	1	1.7	1	1
	B. Chemosis	2	2	1	1	3	2	1	1	2.3	2	1	0.7
	C. Discharge	2	1	0	0	2	1	0	0	2	0.7	0	0
	Weighted score: (A+B+C) x 2 = Total maximum score of 20	10	8	4	4	12	10	4	4	10	8	4	2
Cornea	A.Opacity-degree of density	0	0	0	0	0	0	0	0	0	0	0	0
	B. Area of cornea invloved	0	0	0	0	0	0	0	0	0	0	0	0
	Weighted score: (AxBx5) = Total maximum score of 80	0	0	0	0	0	0	0	0	0	0	0	0
Iris	A	0	0	0	0	0	0	0	0	0	0	0	0
	Weighted scores: Ax5 = Total maximum =10	0	0	0	0	0	0	0	0	0	0	0	0
Total possible maximum = Sum of total maximum scores		10	8	4	4	12	10	4	4	10.6	8.8	4	3.4

H: hours(s)

Iris: 0 – 2 numerical scores

Redness and discharge: 0 – 3 numerical scores

Chemosis, opacity-degree of density and area of cornea involved: 0-4 numerical scores

The total possible maximum score is the sum of all scores obtained for the cornea, iris & conjunctivae.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study the test item did not produce any evidence of ocular corrosivity but a reversible mild irritation was observed. However, the test item does not meet the criteria for classification according to the Globally Harmonized Classification System or according to the Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

OECD 405 – 2019: Three healthy female New Zealand White rabbits free from evidence of ocular irritation and corneal abnormalities, were used in the study. A volume of 0.1 mL of undiluted test item was instilled into the conjunctival sac of each animal (3 female rabbits). The upper and lower eyelids were held for  about one second in order to prevent loss of the test item. Ocular reactions for cornea, iris and conjunctiva of the tested eyes were observed at 1, 24, 48 and 72 hours after test item application and scored according to the method of Draize. The control eyes were observed at the same time periods. A 2% aq solution of Sodium fluorescein dye was instilled into the tested eyes 24h after application and then the stained area of the cornea was observed.  All of the tested eyes were photographed at the 24 hours after application. Ocular reaction was irreversible after 72 hours, therefore observation was extended to 7 days after application.

At 1 hour after application, slight conjunctival redness (score: 1), moderate conjunctival swelling (chemosis, score 3), slight conjunctival swelling (score 2), and moderate discharge (score 2) were observed in 3, 1, 2 & 3 test eyes, respectively.

At 24 hour after application, moderate conjunctival redness (score 2), slight conjunctival redness, slight conjunctival swelling and slight discharge (score 1) were observed in 3, 1, 2 & 3 test eyes, respectively.  The discharged disappeared in one animal at 24 hour post application.

At 48 hours post application, ocular irritation was reduced; slight conjunctival redness and slight conjunctival swelling were found in 3 test eyes and discharge in the tested eyes had disappeared.

At 72 hour post application; slight conjunctival redness and slight conjunctival swelling were found in 3 and 2 test eyes, respectively, and the conjunctival swelling disappeared in 1 test eye.

At 7 day post application, the ocular irritation on the test eyes had completely disappeared. No abnormalities were observed in cornea and iris of any of the tested eyes.

It can be concluded that the observed ocular reactions were reversible, therefore, the test item was considered a mild irritant in the categories of the Harmonised integrated classifications system for human health and environmental hazards of chemical substances and mixtures (OEC Series on Testing and Assessment Number 33) to the rabbit eyes under the study conditions.

Under the conditions of the study the test item did not produce any evidence of ocular corrosivity but a reversible (within 7 days) mild irritation was observed. However, the test item does not meet the criteria for classification according to the Globally Harmonized Classification System or according to the Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.