Registration Dossier

Administrative data

Description of key information

Based on the available in vivo and in vitro data the following conclusion can be drawn: reaction mass of potassium methylsiliconate  is not irritating to the skin but is expected to cause serious eye damage.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 14-29, 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline and in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 23 weeks old
- Weight at study initiation: >2 kg
- Housing: semi-barrier in an air-conditioned room, ABS-plastic rabbit cages, floor 4200 cm²
- Diet (e.g. ad libitum): free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): artificial light, sequence being 12 hours light, 12 hours dark
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
A dose of 0.5 g of the test item was applied to each test site.
Duration of treatment / exposure:
The test item was held in contact with the skin throughout a 4-hour period.
At the end of the exposure period, the residual test item was removed with tap water.
Observation period:
All animals were observed for 72 hours after the patch removal.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm²
- Type of wrap if used: The gauze was held in place with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the residual test item was removed with tap water.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
- Erythema and Eschar Formation
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well defined erythema
3: Moderate to severe erythema
4: Severe erythema (beef redness) to eschar formation preventing grading of erythema
- Oedema Formation
0: No oedema
1: Very slight oedema (barely perceptible)
2: Slight oedema (edges of area well defined by definite raising)
3: Moderate oedema (raised approximately 1 mm)
4: Severe oedema (raised more than 1 mm and extending beyond exposure area)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: mean 24-72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animals #1-3
Time point:
other: mean 24-72 hours
Score:
0.11
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animals #1-3
Time point:
other: mean 24-72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No irritant or corrosive effects were observed on the intact skin of the three female rabbits (strain NZW) after a contact time of 4 hours.
In animal no 3 the test item showed slightly irritant (erythema grade 1) effects 48 hours after patch removal which were fully reversible within 72 hours.
Other effects:
Neither mortalities nor significant clinical signs of toxicity were observed.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present study, the single dermal application of the test item at a dose of 0.5 g showed slightly irritant but no corrosive
effects which were fully reversible within 72 hours after patch removal in one out of three animals. Neither irritant nor corrosive effects were observed in any other animal. Neither mortalities nor significant clinical signs of toxicity were observed.

In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001/59/EC, the test item does not have to be classified and has no obligatory labelling requirement for skin irritation.
According to Annex I of Regulation (EC) 1272/2008, the test item does not have to be classified and has no obligatory labelling requirement for skin irritation.
According to GHS (Globally Harmonized Classification System), the test item has no obligatory labelling requirement for skin irritation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 13-15, 2014
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Amount / concentration applied:
Enough test substance to cover the whole cornea was applied directly onto the cornea by removing the window-locking ring and glass window prior to treatment and moistened with physiological saline 0.9%.
Details on study design:
TEST GROUPS:
- 3 corneas for the test item
- 3 corneas as negative controls treated with physiological saline 0.9% NaCl
- 3 corneas as positive control treated with imidazole 20% in physiological saline 0.9% NaCl


SCORING SYSTEM (Evaluation of the BCOP Assay):

The IVIS cut-off values for identifying test substances as inducing serious eye damage (UN GHS Category 1) and test substances not requiring classification for eye irritation or serious eye damage (UN GHS No Category) are as fllows:

- Mean score ≤ 3: no category
- Mean score >3; ≤ 55: no prediction can be made
- Mean score >55: Category 1

An identification of test substances that should be classified as irritating to eyes (UN GHS Category 2 or Category 2A) or test substances that should be classified as mildly irritating to eyes (UN GHS Category 2B) cannot be made.
Irritation parameter:
other: bovine corneal opacity and permeability
Time point:
other: not applicable
Score:
313.15
Reversibility:
other: not applicable
Remarks on result:
other: in-vitro test
Irritant / corrosive response data:
The eye irritancy potential of the test item was investigated in the bovine corneal opacity and permeability assay. The test item was tested as provided by the sponsor. The following mean in vitro irritation score was calculated: 313.15.

Therefore the test item was classified into UN GHS Category 1.

The in vitro irritation score obtained with the positive control fell within the two standard deviations of the current historical mean and therefore this assay is considered to be valid.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
According to the evaluation criteria the test item is classified into UN GHS Category 1.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The substance is a multi-constituent substance containing methylsilanetriolate, dimers and trimers of methylsilanetriolate, and potassium hydroxide. The substance dissolves in contact with water resulting in an aqueous alkaline solution (pH 13-14) with corrosive properties.


Effects on eye irritation: corrosive

Justification for classification or non-classification

Based on the available data of the substance as supplied, reaction mass of potassium methylsiliconate is classified as R41 "Risk of serious damage to eyes" according to the criteria of EU Directive 67/548/EEC and "Eye Dam. Cat. 1" under Regulation 1272/2008.