Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1998-07-07 - 1998-12-30
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented study in compliance with GLP (conducted with a read-across substance)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Department of Health of the Government of the United Kingdom

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: viscous liquid
Details on test material:
- Molecular formula (if other than submission substance): C28H62NO4P (for a representative structure: Phosphoric acid, di(C8)ester, compds with C12 amine)
- Molecular weight (if other than submission substance): 507.76
- Smiles notation (if other than submission substance): CCCCCCCCCCCCN.O=P(O)(OCCCCCCCC)OCCCCCCCC
- InChl (if other than submission substance): InChI=1/C12H27N/c1-2-3-4-5-6-7-8-9-10-11-12-13/h2-13H2,1H3
- Physical state: extremely pale straw coloured viscous liquid
- Storage condition of test material: room temperature in the dark
- Other: Data relating to the identity, purity and stability of the test material are the responsibility of the Sponsor. The test material is an extremely pale straw coloured viscous liquid.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks
- Weight at study initiation: 2.53 to 2.84 kg
- Housing: individually housed in suspended metal cages
- Diet/Water (e.g. ad libitum): free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 21
- Humidity (%): 65 to 74
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light and twelve hours darkness

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Left eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
single application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Method by Draize, J.H. (1977)

TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 1
Time point:
other: 24h, 48h, 72h
Score:
ca. 0.67
Max. score:
1
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal: 2
Time point:
other: 24h, 48h, 72h
Score:
ca. 1.33
Max. score:
2
Reversibility:
other: not applicable
Remarks on result:
other: animal killed after 72 h observation
Irritation parameter:
cornea opacity score
Basis:
animal: 3
Time point:
other: 24h, 48h, 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal: 1
Time point:
other: 24h, 48h, 72h
Score:
ca. 0.33
Max. score:
1
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal: 2
Time point:
other: 24h, 48h, 72h
Score:
1
Max. score:
1
Reversibility:
other: not applicable
Remarks on result:
other: animal killed after 72 h observation
Irritation parameter:
iris score
Basis:
animal: 3
Time point:
other: 24h, 48h, 72h
Score:
ca. 0.67
Max. score:
1
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal: 1
Time point:
other: 24h, 48h, 72h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal: 2
Time point:
other: 24h, 48h, 72h
Score:
3
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: animal killed after 72 h observation
Irritation parameter:
conjunctivae score
Basis:
animal: 3
Time point:
other: 24h, 48h, 72h
Score:
ca. 2.33
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal: 1
Time point:
other: 24h, 48h, 72h
Score:
ca. 1.33
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal: 2
Time point:
other: 24h, 48h, 72h
Score:
ca. 2.33
Max. score:
3
Reversibility:
other: not applicable
Remarks on result:
other: animal killed after 72 h observation
Irritation parameter:
chemosis score
Basis:
animal: 3
Time point:
other: 24h, 48h, 72h
Score:
ca. 1.67
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritant / corrosive response data:
Under the conditions of this test, the test item was considered to be irritating to the eye.

Any other information on results incl. tables

Interpretation of Results

Classification According to a Modified Version of the Kay and Calandra System

The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of opacity). For each tissue the score was calculated as follows:

Score for conjunctivae = ( A + B + C ) x 2

Score for iris = D x 5

Score for cornea = ( E x F ) x 5

Using the numerical data obtained a modified version of the system described by Kay J H and Calandra J C, 1. SOC. Cosmet. Chem., 1962 13

281-289 was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material. If any rabbit shows irreversible ocular damage the test material will be classified as corrosive to the eye.

Results

Individual and group mean scores for ocular irritation are given. Dulling of the normal lustre of the cornea was noted in two treated eyes one hour after treatment. Diffuse corneal opacity was noted in all treated eyes at the 24 and 48-hour observations. Translucent corneal opacity was noted in one treated eye with diffuse corneal opacity in one other treated eye at the 72-hour observation.

Iridial inflammation was noted in all treated eyes one hour after treatment and at the 24-hour observation, in two treated eyes at the 48-hour observation and persisted in one treated eye at the 72-hour observation.

Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with severe conjunctival irritation in all treated eyes at the 24-hour observation. Severe conjunctival irritation was noted in one treated eye with moderate conjunctiva irritation in two treated eyes at the 48 and 72-hour observations. One animal was killed for humane reasons, immediately after the 72-hour observation, due to the severity of the reactions noted, in accordance with Safepharm company policy and current UK Home Office guidelines. The two remaining treated eyes appeared normal at the 7-day observation.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Mean scores at the 24, 48 and 72 h readings for cornea opacity of the three tested animals amount to 0.67, 1.33 and 1, respectively, according to the method of Draize. Iritis mean scores of 0.33, 1.0 and 0.67 and conjunctivae mean scores of 2.0, 3.0 and 2.33 were yielded for the test animals, respectively. Chemosis mean scores of 1.33, 2.33 and 1.67 are reported for the three tested animals, respectively. However, one animal had very severe effects resulting in its termination at 72-h time point. The effects in this animal are considered to be irreversible and therefore the substance is classified as seriously damaging to eyes (Category 1) according to Regulation (EC) No 1272/2008.
Executive summary:

According to OECD Guideline 405, a study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit in compliance with GLP. Local eye effects were observed 1 h, 24 h, 48 h, 72 h and 7 d after test material application and evaluated by the method of Draize (1977) and by the modified Kay and Calandra classification system. A single instillation (0.1 mL) of phosphoric acid, mono- and di-(C8 -C10) ester, compds. with C12 -14 amine to the non-irrigated eye of three rabbits produced diffuse to translucent corneal opacity, iridial inflammation and severe conjunctival irritation. One animal was killed for humane reasons, immediately after the 72-hour observation. The remaining treated eyes appeared normal at the 7-day observation. The test material produced a maximum group mean score of 35.0 and was classified as at least a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The test material was also considered to be irritant according to EU labelling regulations. It is reasonable to assume that the symbol "Xi", the indication of danger "irritant" and the highest risk phrase R 41 "RISK OF SERIOUS DAMAGE TO EYES" are therefore required.