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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1981 - 1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Justification for type of information:
Refer chapter 13 for detailed read across justification

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: Organisation for Economic Co-operation and Development (1979). OECD Short-term and Long-term Toxicology Groups, Final Report: Acute Eye Irritation/Corrosivity. 31 December, p. 40.
Deviations:
not specified
Qualifier:
according to
Guideline:
other: Association Francaise de Normalisation (1982). Evaluation de I’lrritation et/ou de la Corrosion Oculaires, chez le Lapin. AFNOR (Project): TD3-B dot. 37
Deviations:
not specified
Qualifier:
according to
Guideline:
other: Jownal OJiciel de la R+ptrblique Franwise (1973). MCthodes officielles d’analyse des cosmttiques et produits de beaute. Annexe II: Mtthode ofiicielle pour la determination de I’irritation oculaire. Arrett du I6 Avril 1973. Journal O$icie/ 5 June, p. 3953.
Deviations:
yes
Remarks:
The substance being solid was ground, to produce a fine dust for instillation, which was considered a deviation, as this particluar protocol specifies 20%, (w/v) aqueous dilution of powders.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Appearance: white powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Male albino rabbits of the New Zealand strain, weighing about 2.5 kg and obtained from Roucher SA, Couhe were tested in groups of six.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
100 mg
Details on study design:
REMOVAL OF TEST SUBSTANCE
Rinsing, when required, was generally carried out with Dacryoserum (from Chibret Laboratories, Paris), a solution of boric acid (1.8 g), sodium borate (1.2 g), sodium chloride (0.3 g) and phenylmercury borate (0.002 g) in 100 ml rose distilled water QSP.

SCORING SYSTEM:
Since the Cosmetic and OECD protocols specify no numerical system for the scoring and interpretation of results, a scoring system based on the AFNOR recommendations
was used throughout, with modifications where appropriate to enable direct comparisons between the protocols to be made.
At each observation time, lesions of the conjunctiva, iris and cornea were scored separately using a numerical system based on that of Kay & Calandra (1962), the sum of these scores being the individual ocular irritation index (IOI) for each animal. Calculation of the mean (and standard deviation) of the IOI values obtained at any one time gave the mean occular irritation index (MOI). The greatest MOI obtained over the range of observation times was identified as the acute ocular irritation index (AOI), which was used for the preliminary classification of a substance in one of six categories between ‘non-irritant’ and ‘extremely irritant’. In the AFNOR interpretation,
which takes into account not only the maximum intensity of the lesion but also its reversibility, the preliminary classification is modified if recovery is not virtually complete within 4 days by evaluating the fall in MOI with time and, after 7 days, the frequency of the persisting lesions. The classification resulting from the use of this procedure was therefore compared with that obtained directly from the AOI (corresponding to the OECD approach).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: Acute ocular irritation index (AOI) and mean ocular irritation index (MOI)
Basis:
mean
Time point:
7 d
Score:
62.33
Remarks on result:
other: Rinsing was not done. As the scoring was not possible, the indices were calculated using the maximum scores for the respective parameter.
Irritation parameter:
other: Acute ocular irritation index (AOI) and mean ocular irritation index (MOI)
Basis:
mean
Time point:
7 d
Score:
59
Remarks on result:
other: Rinsing was not done. As the scoring was not possible, the indices were calculated using the minimum scores for the respective parameter.
Irritation parameter:
other: Acute ocular irritation index (AOI)
Basis:
mean
Time point:
7 d
Score:
37
Remarks on result:
other: Rinsing 30 seconds after instillation
Irritation parameter:
other: mean ocular irritation index (MOI)
Basis:
mean
Time point:
7 d
Score:
33
Remarks on result:
other: Rinsing after 30 seconds after instillation
Irritation parameter:
other: Acute ocular irritation index (AOI)
Basis:
mean
Time point:
7 d
Score:
35.17
Remarks on result:
other: Rinsing 4 seconds after instillation
Irritation parameter:
other: mean ocular irritation index (MOI)
Basis:
mean
Time point:
7 d
Score:
14.83
Remarks on result:
other: Rinsing 4 seconds after instillation
Irritation parameter:
other: IO1 = individual ocular irritation index (IOI)
Basis:
mean
Time point:
48 h
Score:
> 30
Remarks on result:
other: Rinsing 4 seconds after instillation

Any other information on results incl. tables

In the test without rinsing, the lesions in the eye and related structures were so severe that correct reading was sometimes impossible. In these cases, two calculations were made to give a minimum value, based on the assumption that all the impossible readings were negative (= 0), and a maximum value, derived from assuming the highest possible score for each of these readings. Of course the irritation classification was determined from the second value. The animals treated in this phase were killed after Day 7 because of the severity of the lesions.

Tests with rinsing. Rinsing at 30 seconds, lead to the irritation remaining relatively significant, with corneal opacity persisting for at least the first few days following instillation.

Rinsing 4 seconds after instillation further reduced the severity of findings.

Based on the above findings, sodium fluorosilicate was classified to be extremely irritant by AFNOR and as severely irritant by OECD.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Sodium fluorosilicate was classified to be as severely irritant according to OECD guideline.
Executive summary:

The eye irritation potential of the sodium fluorosilicate was evaluated in this study. In the first phase, the test substance was instilled into the lower conjunctival cul-de-sac of one eye of each rabbit; the other eye constituted the control. The substance was instilled in a dose of 100 mg weighed on a Mettler balance, type PL 200 (d = 1 mg). Observations were recorded at 1 hour and 1, 2, 3 and 4 and 7 days after instillation and in cases where lesions persisted, also at later stages. As the test substance lead to irritancy more severe than that classified as slightly irritant in the first test, a second phase was carried out where the test substance was similarly instilled into another group of six rabbits, and the eyeball and related structures were rinsed 30 seconds after the instillation. As the material was still found to be irritant, a third test was run with rinsing after 4 sec. Approximately 20 ml of the rinsing solution, at about 20°C was applied to the test eye and to the control using a plastic wash-bottle. Excess liquid was removed with sterile gauze.

In the test without rinsing, the lesions in the eye and related structures were so severe that correct reading was sometimes impossible. In these cases, two calculations were made to give a minimum value, based on the assumption that all the impossible readings were negative (= 0), and a maximum value, derived from assuming .the highest possible score for each of these readings. The irritation classification was determined from the second value. The animals treated in this phase were killed after Day 7 because of the severity of the lesions. Rinsing at 30 seconds, lead to the irritation remaining relatively significant, with corneal opacity persisting for at least the first few days following instillation. Rinsing 4 seconds after instillation further reduced the severity of findings.

Based on the above findings, sodium fluorosilicate was classified to be extremely irritant according to AFNOR guideline and as severely irritant according to OECD guideline.