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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Remarks:
Study was performed prior to the update of the REACH Regulation and prior to the validation of in vitro test methods.
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
The study was performed between 12 May 2010 and 21 May 2010.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of GLP inspection: 15/09/2009 Date of Signature on GLP certificate: 26/11/2009

Test material

Constituent 1
Chemical structure
Reference substance name:
Aluminium orthophosphate
EC Number:
232-056-9
EC Name:
Aluminium orthophosphate
Cas Number:
7784-30-7
Molecular formula:
Al.H3O4P
IUPAC Name:
[phosphato(3-)-kappa~3~O,O',O'']aluminum
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Sponsor's identification: Aluminium orthophosphate
Description: white powder
Batch number: A88770A
Date received: 28 August 2009
Expiry date: 05 June 2010
Storage conditions: room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Loughborough, UK.

- Age at study initiation: Twelve to twenty weeks old

- Weight at study initiation: 2.31 to 2.47 kg

- Housing: The animals were individually housed in suspended cages. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

- Diet (e.g. ad libitum): ad libitum (2030 Teklad Global Rabbit diet supplied by Harlan Laboratories U.K. Ltd., Oxon, UK)

- Water (e.g. ad libitum): ad libitum.

- Acclimation period: At least five days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 17 to 23°C

- Humidity (%): 30 to 70%

- Air changes (per hr): At least fifteen changes per hour

- Photoperiod (hrs dark / hrs light): Twelve hours continuous light (06:00 to 18:00) and twelve hours darkness


IN-LIFE DATES: From: day 1 To:day 3

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes.
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 98 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.

- Concentration (if solution): Undiluted and used as supplied


Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.
Number of animals or in vitro replicates:
2 animals were tested in total. (After consideration of the ocular responses produced in the first treated animal, one additional animals was treated. )

Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done):
Not applicable

- Time after start of exposure:
Not applicable


SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation given in Appendix 2, (from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).


TOOL USED TO ASSESS SCORE:

Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 69198 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
cornea opacity score
Basis:
animal: 69234 Male
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Irritation parameter:
iris score
Basis:
animal: 69198 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: No effect observed
Irritation parameter:
iris score
Basis:
animal: 69234 Male
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: No effect observed
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 69198 Male
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal: 69234 Male
Time point:
24/48/72 h
Score:
0.66
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal: 69198 Male
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal: 69234 Male
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.
No corneal or iridial effects were noted during the test.
Moderate conjunctival irritation was noted in both treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24 and 48-Hour observations.
Both treated eyes appeared normal at the 72-Hour observation.
Other effects:
Body weight
Both animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Interpretation of Results

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 cornea involved). 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 ( Modified Kay and Calandra Interpretation of Eye Irritation Test 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 evidence of irreversible ocular damage is noted, the test material will be classified as corrosive to the eye.

Table1               IndividualScores and Individual Total Scoresfor Ocular Irritation

Rabbit Number and Sex

69198 Male

69234 Male

IPR= 2

IPR = 2

Time After Treatment

1
Hour

24
Hours

48
Hours

72
Hours

1
Hour

24
Hours

48
Hours

72
Hours

CORNEA

 

 

 

 

 

 

 

 

E = Degree of Opacity

0

0

0

0

0

0

0

0

F = Area of Cornea Involved

0

0

0

0

0

0

0

0

Score (E x F) x 5

0

0

0

0

0

0

0

0

IRIS

 

 

 

 

 

 

 

 

D

0

0

0

0

0

0

0

0

Score (D x 5)

0

0

0

0

0

0

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

A = Redness

2

1

1

0

2

1

1

0

B = Chemosis

2

1

0

0

2

1

0

0

C = Discharge

2

1

0

0

2

1

0

0

Score (A + B + C) x 2

12

6

2

0

12

6

2

0

Total Score

12

6

2

0

12

6

2

0

 

IPR=  Initial pain reaction

Table 2               Individual Total Scores and Group Mean Scoresfor Ocular Irritation

Rabbit Number

and Sex

Individual Total Scores At:

1 Hour

24 Hours

48 Hours

72 Hours

69198 Male

12

6

2

0

69234 Male

12

6

2

0

Group Total

24

12

4

0

Group Mean Score

12.0

6.0

2.0

0.0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test material did not meet the criteria for classification as irritant according to Regulation (EC) No. 1272/2008 (EU CLP). This study is conducted according to the appropriate guidelines (EU ) and under the conditions of GLP and therefore the study is considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint. Study is sufficient for classification and labelling purposes, in accordance with Regulation (EC) No. 1272/2008 (EU CLP).
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 24 April 2002)

 Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

Result. A single application of the test material to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. Both treated eyes appeared normal at the 72-Hour observation.

Conclusion. The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.