[No public or meaningful name is available]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-05-30 to 2007-06-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted April 24, 2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

April 29, 2004

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

1

Reference substance name:

Reaction products of DL-methionine and C18 unsaturated fatty acid chloride and isopropanol

Molecular formula:

not applicable (UVCB)

IUPAC Name:

Reaction products of DL-methionine and C18 unsaturated fatty acid chloride and isopropanol

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 07SK021
- Description: Liquid, dark brownish
- Expiration date of the lot/batch: n.a.
- Purity test date: 94%
- Expiry date: March 2009

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature (range of 20 ± 5° C), light protected

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Netherlands BV, Kreuzelweg 53, NL-5961 NM Horst / The Netherlands
Postbus 6174, NL-5960 AD Horst / The Netherlands

- Age at study initiation: one male12 weeks; two females 13 weeks
- Weight at Day1 of treatment: females 2044 g and 2500 g, male 2373 g
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: yes

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 10-15
- Photoperiod: 12 hrs dark / 12 hrs light

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 mL

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48, 72 hours, as well as 7, 10, 14 and 21 days after administration.

Number of animals or in vitro replicates:

3 (one male two females)

Details on study design:

On the day of treatment, 0.1 mL of DODICOR V 5654 was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of test item. The right eye remained untreated and served as the reference control.

REMOVAL OF TEST SUBSTANCE

- Washing (if done): no

SCORING SYSTEM: The eye reactions were assessed according to the numerical scoring system listed in the Commission Directive 2004/73/EC, April 29, 2004

TOOL USED TO ASSESS SCORE: hand-slit lamp (Cliptrix diagnostic-lamp)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible

Results 4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 21 days

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 21 day

Remarks on result:

probability of moderate irritation

Remarks:

At day 21 reading the score was still 1.

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible

Results 8

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible

Results 9

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 14 days

Results 10

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible

Results 11

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

1.19

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Remarks:

At 21 day reading in one animal conjunctiva reddining was still present.

Remarks on result:

probability of moderate irritation

Remarks:

The test item did not induce significant or irreversible damage to the rabbit eye.

Any other information on results incl. tables

TABLE 1:       EYE IRRITATION SCORES - MEAN VALUES AFTER 24, 48 AND 72 HOURS

 

Animal Number	Sex	Corneal Opacity	N	Iris	N	Conjunctivae
						Redness	N	Chemosis	N
4	M	0.00	3	0.00	3	2.00		1.33	3
5	F	1.00	3	0.00	3	2.00		1.33	3
6	F	0.67	3	0.00	3	1.67		0.67	3

N = number of available data points

Applicant's summary and conclusion

Interpretation of results:

other: Cat 2 (irritating to eyes) based on CLP criteria

Conclusions:

Based on the results of a.m. study, Dodicor V 5654 is irritating to the eye.

Executive summary:

The primary eye irritation potential of DODICOR V 5654 was investigated according toOECD test guideline no. 405. The test item was applied by instillation of 0.1 mL into the lefteye of each of three young adult New Zealand White rabbits. Scoring of irritation effects wasperformed approximately 1, 24, 48 and 72 hours, as well as 7, 10, 14 and 21 days after testitem instillation.The mean score was calculated across 3 scoring times (24, 48 and 72 hours afterinstillation) for each animal for corneal opacity, iris, redness and chemosis of theconjunctivae, separately. The individual mean scores for corneal opacity were 0.00, 1.00 and0.67, respectively and for iris 0.00 for each of all three animals. The individual mean scores for the conjunctivae were 2.00, 2.00 and 1.67 for reddening and 1.33, 1.33 and 0.67 forchemosis, respectively.

The instillation of DODICOR V 5654 into the eye resulted in mild to moderate, early-onsetocular changes, such as corneal opacity, reddening of the conjunctivae and sclerae,conjunctival swelling and discharge. The severity of the local reactions decreased throughthe 22 days of observation and the study was closed with a slight conjunctival redness in oneanimal.No abnormal findings were observed in the 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 by the test item was observed and no clinical signs were observed.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye.