Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 September 2007 to 1 October 2007.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of inspection: 30 August 2005 Date of Signature: 21 November 2005

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 3-Octadecyloxypropyl-N,N,N-trimethylammonium chloride
- Molecular formula (if other than submission substance): Not applicable
- Molecular weight (if other than submission substance): Not applicable
- Smiles notation (if other than submission substance): Not applicable
- InChl (if other than submission substance): Not applicable
- Structural formula attached as image file (if other than submission substance): Not applicable
- Substance type: white solid
- Physical state: solid
- Analytical purity: Not reported
- Impurities (identity and concentrations): Not reported
- Composition of test material, percentage of components: Not reported
- Isomers composition: Not reported
- Purity test date: Not reported
- Lot/batch No.: Exp. I-070518
- Expiration date of the lot/batch: Not reported
- Radiochemical purity (if radiolabelling): Not applicable
- Specific activity (if radiolabelling): Not applicable
- Locations of the label (if radiolabelling): Not applicable
- Expiration date of radiochemical substance (if radiolabelling): Not applicable
- Stability under test conditions: Not reported.
- Storage condition of test material: room temperature in the dark.
- Other: Not reported.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: New Zealand White rabbits were supplied by an accredited supplier.
- Age at study initiation: Twelve to 20 weeks old.
- Weight at study initiation: 2.59 kg.
- Housing: The animal was housed in suspended cages.
- Diet (e.g. ad libitum): Certified Rabbit Diet ad libitum throughout the study.
- Water (e.g. ad libitum): Mains drinking water ad libitum throughout the study.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 changes per hour.
- Photoperiod (hrs dark / hrs light): Twelve hours continuous light (06:00 to 18:00) and 12 hours darkness.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye in the exposured animal was used for control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A volume of 0.1 ml of the test material, which was found to weigh approximately 67 mg.

VEHICLE
Not applicable.
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not applicable

SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following the grading in the test guideline. The result was classified according to EU classification system.

TOOL USED TO ASSESS SCORE: A standard ophthalmoscope.

OTHERS
Immediately before the start of the test, both eyes of the provisionally selected test rabbit were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. An animal free of ocular damage was used. Immediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale shown in Table 1. After consideration of the ocular responses produced in this animal, no additional animals were treated.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 66576 Male
Time point:
other: mean at 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
not reversible
Remarks on result:
other: Max score was observed at 24, 48 and 72 hours
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
animal: 66576 Male
Time point:
other: mean of 24, 48 and 72 hours
Score:
2
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: Max score was observed at 24, 48 and 72 hours
Irritation parameter:
chemosis score
Basis:
animal: 66576 Male
Time point:
other: mean at 24, 48 and 72 hours
Score:
2.7
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: Max score was observed at 24 and 48 hours
Irritant / corrosive response data:
Individual scores for ocular irritation are given in Table 2.
Scattered or diffuse corneal opacity and iridial inflammation were noted in the treated eye one hour after treatment and at subsequent observations. Vascularisation, with a generalised ingrowth of vessels for approximately 3 mm, was noted in the treated eye at the 14 and 21-day observations.
Severe conjunctival irritation was noted in the treated eye one hour after treatment and at the 24 and 48 hour observations with moderate conjunctival irritation at the 72-hour, 7, 14 and 21 day observations.
A pale area covering the nictitating membrane was noted in the treated eye at the 24, 48, 72 hour, 7 and 14-day observations. A small area of haemorrhage on the upper and lower area of nictitating membrane was noted in the treated eye at the 72 hour, 7, 14 and 21-day observations. Ectropion was noted in the treated eye at the 14 and 21-day observations.
The persistence of reactions in the treated eye at the 21 day observation was considered to be indicative of irreversible ocular damage.
Other effects:
Not reported.

Any other information on results incl. tables

Table 2 Individual Scoresfor Ocular Irritation

Rabbit Number and Sex

66576 Male

IPR= 3

Time After Treatment

1 Hour

24 Hours

48 Hours

72 Hours

7 Days

14 Days

21 Days

CORNEA

 

 

 

 

 

 

 

Degree of Opacity

1

1

1

1

1

1V

1V

Area of Cornea Involved

4

4

4

4

4

4

4

IRIS

1

1

1

1

1

1

1

CONJUNCTIVA

 

 

 

 

 

 

 

Redness

2

2

2

2

2

2

2

Chemosis

3

3

3

2

2

2

2

Discharge

3

3

3

2

2

2

2

Other

 

P

P

PH

PH

PHEc

HEc

IPR= Initial pain reaction                  

H = Small area of haemorrhage on upper and lower area of nictitating membrane                   

P = Pale area covering nictitating membrane

V = Vascularisation, with a generalised ingrowth of vessels, approximately 3 mm in length                                                 

Ec = Ectropion

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced irreversible ocular damage and was considered to be CORROSIVE to the rabbit eye (based on one rabbit only). The test substance is classified as R41 Risk of serious damage to eyes under Council Directive 67/548/EEC and Category 1 H318: cause serious eye damage under Regulation (EC) No 1272/2008.
Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted)

§        Method B5 Acute Toxicity (Eye Irritation) of Commission Directive 2004/73/EC

Result. A single application of the test material to the non-irrigated eye of one rabbit produced  scattered or diffuse corneal opacity, iridial inflammation and severe conjunctival irritation. Other ocular effects noted were vascularisation, with a generalised ingrowth of vessels for approximately 3 mm, a pale area covering the nictitating membrane, a small area of haemorrhage on upper and lower area of nictitating membrane and ectropion. The persistence of reactions in the treated eye at the 21‑day observation was considered to be indicative of irreversible ocular damage.

Conclusion. The test material produced irreversible ocular damage and was considered to be CORROSIVE to the rabbit eye (based on one rabbit only). The test substance is classified as R41 Risk of serious damage to eyes under Council Directive 67/548/EEC and Category 1 H318: cause serious eye damage under Regulation (EC) No 1272/2008.