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Description of key information

A skin irritation study and an eye irritation study were conducted in rabbits with the test substance disodium disilicate (delta-crystalline). The dermal irritation study showed that the test substance is not irritating to skin and the eye irritation study showed that the test substance is severely irritating to the eye to such extend that the study had to be aborted after 24 hours. In an in vivo eye irritation study the test item was applied a 10% solution in sodium sulphate. Slight to severe conjunctivae irritant effects (conjunctival oedema) were observed in 2 animals, which were fully reversible within 1 week. At this concentration, classification as eye irritant was not warranted.

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:
1987-05-19 until 1987-05-22
Reliability:
1 (reliable without restriction)
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
, adopted: 12 May 1981
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
, directive 84/449/EWG
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund
- Age at study initiation: About 3-5 months
- Weight at study initiation: 2.4- 3.5 kg
- Housing: In fully air-conditioned rooms, separate cages (arranged in a battery)
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet- rabbits (Altromin GmbH, Lage/Lippe), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): Water from automatic water dispensers, ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 50- 20%
- Photoperiod (hrs dark / hrs light): Lighting time: 12 hours daily


Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
physiological saline
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: 0.5 g of the test substance
The amount applied (0.5 g) was pasted with 0.2 mL isotonic saline.
Duration of treatment / exposure:
4 hours
Observation period:
30-60 minutes and 24, 48, 72 hours after removal of the patches.
Number of animals:
3 rabbits
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: The substance was applied over the whole surface of a cellulose patch on a piece of surgical plaster (specially produced by Beiersdorf AG, Hamburg). The plaster was fixed to the prepared skin area and then covered with a semi-occlusive bandage.

SCORING SYSTEM: The scoring system is as instructed by the relevant guidelines according to the technique of Draize.

REMOVAL OF TEST SUBSTANCE
- After the exposure period (4 hours) all remnants of the test substance were carefully removed from the skin with warm tap water.



Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: The score (0) is a mean value of the results obtained at the time points indicated above for animal # 1.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: The score (0) is a mean value of the results obtained at the time points indicated above for animal # 2.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: The score (0) is a mean value of the results obtained at the time points indicated above for animal # 3.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: The score (0) is a mean value of the results obtained at the time points indicated above for animal # 1.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: The score (0) is a mean value of the results obtained at the time points indicated above for animal # 2.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: The score (0) is a mean value of the results obtained at the time points indicated above for animal # 3.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No signs of irritation were observed during the whole observation period.
Other effects:
No other effects

No remarks

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study disodium disilicate (delta-crystalline) is not irritating to the skin.
Executive summary:

In a primary dermal irritation study (study no.: 94.0712), 3 male and female New Zealand albino rabbits (weight: 2.4 - 3.5 kg, age: 3 - 5 months) were dermally exposed to disodium disilicate (delta-crystalline). 0.5 g of the test substance was pasted with 0.2 mL isotonic saline on a 2.5 cm x 2.5 cm cellulose patch which was fixed in a semi-occlusive dressing for 4 hours. Animals were observed for up to 72 hours after removal of the patches. The study was conducted according to the OECD 404 guideline and the EG guideline B.4 and irritation was scored by the method of DRAIZE.

No cutaneous reactions (edema, erythema or corrssion) were recorded in any of the observation time points (each determined score was 0.0). Thus, under the study conditions the test substance, disodium disilicate (delta-crystalline), in rabbits exhibit no potential as a skin irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1987-05-26 until 1987-05-27
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline study
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 1981-05-12
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
of the Directive 84/449/EEC
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund
- Age of animals: About 3-5 months
- Animal weights: 2.8- 3.8 kg
- Housing: In fully air-conditioned rooms, separate cages (arranged in a battery)
- Diet (e.g. ad libitum): Altromin 2123 maintenance diet- rabbit (Altromin GmbH, Lage/Lippe), ad libitum and hay (approx. 15 g daily)
- Water (e.g. ad libitum): Water from automatic water dispensers, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20± 3°C
- Humidity (%): 50± 20%
- Photoperiod (hrs dark / hrs light): Lighting time: 12 hours daily

IN-LIFE DATES: From: 1987-05-26 To: 1987-05-27
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eyes (the right eyes) of the 3 rabbits served in each case as a control.
Amount / concentration applied:
100 mg disodium disilicate (delta-crystalline) was applied in a single dose.
Duration of treatment / exposure:
Not indicated
Observation period (in vivo):
1 hour and 24 hours after application
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
SCORING SYSTEM: As instructed by the relevant guidelines.

TOOL USED TO ASSESS SCORE: Fluorescein (one drop of 0.01% fluorescein-sodium solution).
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 24h
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 24h
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 24h
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 24h
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 1h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 24h
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 1h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 24h
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 1h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 24h
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1h
Score:
1
Max. score:
2
Reversibility:
not fully reversible within: 24h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 24h
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 24h
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 24h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 24h
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: 24h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 24h
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 24h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24h
Score:
3.33
Max. score:
4
Reversibility:
not fully reversible within: 24h
Irritant / corrosive response data:
Up to 24 hours after application the conjunctivae of the animals showed swellings: The lids were about half closed and a diffuse red beefy colour appeared. Additionally, clear-colourless or white-mocous discharge were noted. One hour after application the iris of all animals was reddened.
24 hours after application the cornea of the animals showed opacity areas, the iris was invisible. The conjunctivae and the nicating membrane were discoloured white. The conjunctival sac showed severe corrosions.
Other effects:
No other effects.

Due to the severe irritation findings, the animals were killled 24 hours after application.

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the study conditions, the test substance applied to the eyes of rabbits was found to be severely irritating to the eyes.
Executive summary:
In a primary eye irritation study (study no.: 94.0713) 100 mg of the test substance disodium disilicate (delta-crystalline) was instilled into the conjunctival sac of three New Zealand albino rabbits (weight: 2.8-3.8 kg, age: 3-5 months) while the untreated eye served in each animal as a control. The study was conducted according to the OECD 405 guideline and the EG guideline B.5. Up to 24 hours after application (the eyes were examined 1 hour and 24 hours after application), the state of the eyes of all animals reached the maximum scores in most of the examined parameters. In addition, a clear- colorless or white-mucous discharge was noted and the conjunctival sac showed severe corrosions. Due to the severe irritation findings the study was terminated after 24 hours and the animals were sacrificed. The test substance is therefore considered to be severely irritating to the eyes under the test conditions, in rabbits.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015-07-27 to 2015-09-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 02 October 2012
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S & K LAP Kft. 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: 11 weeks
- Weight at study initiation: 2660 - 2980 g
- Housing: Animals were housed individually in metal cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days in the first animal, 6 days in the second animal and 7 days in third animal

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12 / 12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
yes
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

CONTROL ITEM:
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:
single treatment
Observation period (in vivo):
1, 24, 48, 72 hours and 1 week after application the irritation scores were recorded
Number of animals or in vitro replicates:
3 males
Details on study design:
Three healthy male animals were selected for the test. Care was taken to select only those animals that had normal eye conditions, any with ocular lesions were rejected. In the first step an initial test was performed using one animal. The test item was applied in a single dose to the left eye of the animal. The sodium sulphate was applied in a single dose to the right eye (control eye) of the same animal. The eyelids were held closed gently for about one second to prevent any loss of the test item. In the initial test a slight to severe conjunctival irritant effect was observed 24 hours after treatment. The confirmatory test was conducted using a second animal. In the second animal a slight irritant effect was observed 24 hours after treatment. A further confirmatory test was conducted using a third animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes of the test animals were not washed out and the test substance/control item was removed from the eye of the test animal by physiological mechanisms.

SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (2nd October 2012), see also Table 1 in box “Any other information on materials & methods incl. tables”.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
positive indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
The test item SKS-6 powder (10% in sodium sulphate) applied to the rabbits' left eye mucosa, caused slight to severe conjunctivae irritant effects during the study. All symptoms were fully reversible within 1 week. For individual results please see Table 2 in box "Any other information on results incl. tables". The control item sodium sulphate applied to the rabbits’ right eye mucosa, caused slight to moderate conjunctivae irritant effects during the study, fully reversible within 48 hours. For individual results please see Table 3 in box "Any other information on results incl. tables".
According to CLP criteria, the test item SKS-6 powder (10% in sodium sulphate) does not to be classified for eye irritation.

Table 2: Individual Eye Irritation Scores, left eye, treated with SKS-6 powder (10% in sodium sulphate)

Animal No. 24 hours 48 hours 72 hours 1 week after treatment Mean 24/48/72 hours
Cornea opacity Iris Conjunctivae  Chemosis Cornea opacity Iris Conjunctivae  Chemosis Cornea opacity Iris Conjunctivae  Chemosis Cornea opacity Iris Conjunctivae  Chemosis Cornea opacity Iris Conjunctivae  Chemosis
1 0 0 1 3 0 0 1 2 0 0 1 1 0 0 0 0 0 0 1 2
2 0 0 0 1 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0,67
3 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

Table 3: Individual Eye Irritation Scores, right eye, treated with sodium sulphate

Animal No. 24 hours 48 hours 72 hours 1 week after treatment Mean 24/48/72 hours
Cornea opacity Iris Conjunctivae  Chemosis Cornea opacity Iris Conjunctivae  Chemosis Cornea opacity Iris Conjunctivae  Chemosis Cornea opacity Iris Conjunctivae  Chemosis Cornea opacity Iris Conjunctivae  Chemosis
1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
2 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
3 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0,33 0
Interpretation of results:
GHS criteria not met
Conclusions:
In a primary eye irritation/corrosion study in rabbits conducted according to OECD 405, the test item SKS-6 powder (10% in sodium sulphate) was tested as not eye irritating.
Executive summary:

In a primary eye irritation study (OECD 405), 0.1 g of the test item SKS-6 powder (10% in sodium sulphate) was instilled into the conjunctival sac of the left eye of young adult New Zealand White rabbits (three males). Sodium sulphate was applied to the right eye (control eye) of the same animals. The treated eyes were not washed, but the test substance/control item was removed from the eye of the test animal by physiological mechanisms. Animals then were observed for 7 days. Irritation was scored by the method of Draize. The test item SKS-6 powder (10% in sodium sulphate) caused slight to severe conjunctivae irritant effects (conjunctival oedema) in 2 animals, which were fully reversible within 1 week. The control sodium sulphate caused slight conjunctivae irritant effects, which were fully reversible within 48 hours. Based on the results, 10% disodium disilicate in sodium sulphate is not an eye irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Additional information

Skin:

In a primary dermal irritation study (study no.: 94.0712), 3 male and female New Zealand albino rabbits (weight: 2.4- 3.5 kg, age: 3-5 months) were dermally exposed to disodium disilicate (delta-crystalline). 0.5 g of the test substance was pasted with 0.2 mL isotonic saline on a 2.5 cm x 2.5 cm cellulose patch which was fixed in a semi-occlusive dressing for 4 hours. Animals were observed for up to 72 hours after removal of the patches. The study was conducted according to the OECD 404 guideline and the EG guideline B.4, irritation was scored by the method of Draize.

No cutaneous reactions (edema, erythema or corrosion) were recorded in any of the observation time points (each given score was 0.0). Thus, under the study conditions the test substance, disodium disilicate (delta-crystalline), does not cause dermal irritation.

 

Eyes:

In a primary eye irritation study (study no.: 94.0713) 100 mg of the test substance disodium disilicate (delta-crystalline) was instilled into the conjunctival sac of three New Zealand albino rabbits (weight: 2.8-3.8 kg, age: 3-5 months) while the untreated eye served in each animal as a control. The study was conducted according to the OECD 405 guideline and the EG guideline B.5.

Up to 24 hours after application (the eyes were examined 1 hour and 24 hours after application), the state of the eyes of all animals reached the maximum scores in most of the examined parameters. In addition, a clear- colourless or white-mucous discharge was noted and the conjunctival sac showed severe corrosions. Due to the severe irritation findings the study was terminated after 24 hours and the animals were sacrificed. The test substance is therefore considered under the test conditions, in rabbits, to be severely irritating to the eyes.

Effects on eye irritation: highly irritating

In a primary eye irritation study (OECD 405, Kuthy 2015), 0.1 g of the diluted test item (10% in sodium sulphate) was instilled into the conjunctival sac of the left eye of young adult New Zealand White rabbits (three males). Sodium sulphate was applied to the right eye (control eye) of the same animals. The treated eyes were not washed, but the test substance/control item was removed from the eye of the test animal by physiological mechanisms. Animals then were observed for 7 days. Irritation was scored by the method of Draize. The test item caused slight to severe conjunctivae irritant effects (conjunctival oedema) in 2 animals, which were fully reversible within 1 week. The control sodium sulphate caused slight conjunctivae irritant effects, which were fully reversible within 48 hours. Based on the results, 10% disodium disilicate in sodium sulphate is not classified as eye irritant. This study was used to setup a specific concentration limit.

Justification for classification or non-classification

Skin:

Based on the results of the presented skin irritation study the test substance is not classified according to the CLP/GHS.

Eyes:

The study was aborted before scheduled (after 24 hours) due to the severe observed indications. The effects were not expected to be reversible and as such fulfilling the criteria for category 1 classification according to CLP. The pH of the test substance in water is 11.5, thus, the study should not be repeated and the test substance disodium disilicate (delta-crystalline) is therefore classified as category 1 with labelling of H318: causes serious eye damage.

Because the test item did not warrant classification when applied as a 10% solution in a primary eye irritation study according to OECD 405, this study was used to setup a specific concentration limit (i.e. no classification below 10% (w/w). In this study, only a single dose was tested. Therefore, it was not possible to derive a concentration threshold for Eye Dam. 1 vs. Eye Irrit. 2 for mixtures exceeding 10%.