Disodium fluorophosphate

Eye irritation

Administrative data

Endpoint:

eye irritation, other

Remarks:

In vivo study performed in accordance with REACH at the time of first submission (2010).

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 27 April 2010 and 08 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:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Date of GLP inspection: Date of Signature on GLP certificate: 26/11/2009

Test material

Test material information

Constituent 1

Reference substance name:

Disodium fluorophosphate

EC Number:

233-433-0

EC Name:

Disodium fluorophosphate

Cas Number:

10163-15-2

Molecular formula:

FH2O3P.2Na

IUPAC Name:

disodium fluorophosphate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Sponsor's identification : Disodium flourophosphate
Description : white solid
Batch number : 9-01941-56
Date received : 12 August 2009
Expiry Date : 31 January 2011
Storage conditions : room temperature in the dark over silica gel

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source:
Harlan Laboratories UK Ltd, Oxon, UK

- Age at study initiation:
Twelve to twenty weeks old

- Weight at study initiation:
2.0 to 3.5 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 UK 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 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

VEHICLE

- Amount(s) applied (volume or weight with unit):
Not applicable

- Concentration (if solution):
Not applicable

- Lot/batch no. (if required):
Not applicable

- Purity:
Not reported

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

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 animal 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

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

Degree of opacity

Basis:

animal: 69147 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks:

No effects observed

Results 2

Irritation parameter:

cornea opacity score

Remarks:

Degree of opacity

Basis:

animal: 69180 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

not specified

Remarks:

No effects observed

Results 3

Irritation parameter:

iris score

Basis:

animal: 69147 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks:

No effects observed

Results 4

Irritation parameter:

iris score

Basis:

animal: 69180 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0

Max. score:

2

Reversibility:

not specified

Remarks:

No effects observed

Results 5

Irritation parameter:

other: redness

Basis:

animal: 69147 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

other: redness

Basis:

animal: 69180 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0.66

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 7

Irritation parameter:

chemosis score

Basis:

animal: 69147 Male

Time point:

other: Mean 24, 48 and 72

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

chemosis score

Basis:

animal: 69180 Male

Time point:

other: Mean 24, 48 and 72 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Ocular Reactions
Individual and group mean scores for ocular irritation are given in Table 1 and Table 2.
No corneal effects were noted during the study.
No iridial inflammation effects were noted during the study.
Moderate conjunctival irritation was noted in all 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
All animals showed expected gain in bodyweight during the study.
Individual bodyweights and bodyweight changes are given in Table 3.

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              Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	69147Male				69180Male
	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
69147Male	12	6	2	0
69180Male	12	6	2	0
Group Total	24	12	4	0
Group Mean Score	12.0	6.0	2.0	0.0

 

Table 3              Individual Bodyweights and Bodyweight Changes

Rabbit Number and Sex	Individual Bodyweight (kg)		Bodyweight Change (kg)
	Day 0	Day 3
69147Male	2.60	2.71	0.11
69180Male	2.15	2.24	0.09

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

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.
The test material is not classified as an eye irritant according to the EU labelling regulations Commision Directive 2001/59/EC. In addition the substance is not classified as irritating to the eyes in accordance with Regulation (EC) No 1272/2008 (EU CLP).

This study has been selected as the key study because the results are sufficient in order to derive a reliable conclusion on classification and labelling 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.