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Administrative data

Description of key information

Regarding skin and eye irritation/corrosion, no data are available on the reaction mass itself. However, data are available on all components of this reaction mass (sodium chloride, sodium carbonate and sodium sulfate).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1954
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data are available for interpretation of results
Qualifier:
no guideline available
Principles of method if other than guideline:
None
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
No data
Type of coverage:
not specified
Preparation of test site:
other: intact and abraded
Vehicle:
water
Remarks:
for 5%, 10%, 20% and 50 % NaCl solution
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Concentration (if solution): 5%, 10%, 20% and 50 % and 100% NaCl
Duration of treatment / exposure:
No data
Observation period:
No data
Number of animals:
No data
Details on study design:
Please see the table below.
Irritation parameter:
other: The following responses were observed: reddening skin, presence or absence of edema, of necrosis and of scarbs.
Basis:
other: Not specified
Time point:
other: Not specified
Reversibility:
not specified
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
When in contact with the intact skin, sodium chloride causes no response, either in undiluted form or in solution. However, abraded skin may be appreciably irritated depending upon the concentration of the salt solution. Strong solutions (20% or better) result in scab and scar formation after a few applications. Weaker solutions (10% or 5%) produce slight irritation which delays healing without scarring.
Other effects:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
When in contact with the intact skin, sodium chloride causes no response, either in undiluted form or in solution. However, abraded skin may be appreciably irritated depending upon the concentration of the salt solution. Strong solutions (20% or better) result in scab and scar formation after a few applications. Weaker solutions (10% or 5%) produce slight irritation which delays healing without scarring.
Executive summary:

When in contact with the intact skin, sodium chloride causes no response, either in undiluted form or in solution. However, abraded skin may be appreciably irritated depending upon the concentration of the salt solution. Strong solutions (20% or better) result in scab and scar formation after a few applications. Weaker solutions (10% or 5%) produce slight irritation which delays healing without scarring.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The report contains sufficient information to permit a meaningful evaluation of study results.
Qualifier:
no guideline available
Principles of method if other than guideline:
The study methodology followed was equivalent or similar to OECD 404.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
not specified in the report
Type of coverage:
not specified
Preparation of test site:
other: intact and abraded skin
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
50 mg dry powder moistened with 0.1 ml water
Duration of treatment / exposure:
single exposure
Observation period:
72 hours
Number of animals:
6 rabbits
Details on study design:
not specified in the report
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0.88
Max. score:
8
Reversibility:
fully reversible within: 72 hours
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
The overall irritation score was 0.88 out of a maximum score of 8
Other effects:
not specified in the report

not applicable

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results, sodium chloride is slightly irritating to rabbit skin but it is not classified as irritating to skin according to UN and EU GHS criteria.


Executive summary:

A primary skin irritation study was conducted in rabbits on intact and abraded skin and based on the results, sodium chloride induce slight irritation to rabbit skin which is fully reversible within 72h. Therefore sodium chloride is not classified for skin irritation according to UN and EU GHS criteria.

 

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study with minor deviations, fully adequate for assessment. In the OECD SIDS on sodium carbonate (2002) a similar reliability was assigned.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Test substance was not moistened with water ; patch was occlusive instead of semi-occlusive. Minor deviations included small differences in housing conditions and no other toxic effects have been observed.
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Sex: Not reported.
- Source: Harald Schriever, Rabbit farm, Germany.
- Age: Not reported.
- Weight at study initiation: 2.4 - 2.6 kg.
- Number of animals: 6
- Controls: Included but not described.
Type of coverage:
occlusive
Vehicle:
other: other
Amount / concentration applied:
Concentration: 0.5 g
Duration of treatment / exposure:
4 hour(s)
Number of animals:
6
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Other effects:
No
Interpretation of results:
GHS criteria not met
Conclusions:
Classification: not irritating for skin.
Executive summary:

In a test performed according to OECD test guideline 404, 0.5 gr of sodium carbonate was applied on the skin of New Zealand White Rabbits. The scores are the following: Erythema score = 0 (24/48/72h). Edema score = 0 (24/48/72h). Based on these results, sodium carbonate is not considered to be irritating to skin.

 

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Type of coverage:
occlusive
Vehicle:
other: polyetyleneglycol 400
Amount / concentration applied:
Concentration: 500 mg
Duration of treatment / exposure:
4 hour(s)
Number of animals:
3
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0

RS-Freetext:
AVERAGE SCORE
- Erythema: score = 0, after 14 days
- Edema: score = 0 after 14 days
REVERSIBILITY: not described
OTHER EFFECTS: Irrit. index : edema = 0.0; erytheme = 0.0.
Body weight, 3.7 - 4.2 kg

Interpretation of results:
GHS criteria not met
Conclusions:
Classification: not irritating for skin.
Executive summary:

In a test performed according to OECD test guideline 404, 500 gr of sodium carbonate was applied on the skin of New Zealand White Rabbits. The scores are the following: Erythema score = 0 (24/48/72h). Edema score = 0 (24/48/72h). Based on these results, disodium sulfate is not considered to be irritating to skin.

 

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1960
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines.
Qualifier:
no guideline available
Principles of method if other than guideline:
None
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or test system and environmental conditions:
No data
Type of coverage:
not specified
Preparation of test site:
other: intact and abraded
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
Undiluted as well as 10% aqueous solution was applied to the rabbit's skin.
Duration of treatment / exposure:
Duration varied from 3 to 10 applications.
Observation period:
21 days
Number of animals:
No data
Details on study design:
TEST SITE
- Area of exposure: Belly and ear
Irritation parameter:
other: The following responses were observed: absence or presence of hyperemia, edema and necrosis.
Basis:
other: Not specifed
Time point:
other: Not specified
Reversibility:
fully reversible within: 21 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
Please see the table above
Other effects:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
To intact skin, undiluted sodium chloride (wet patch) induces slight edema. Dry undiluted sodium chloride induces very slight edema and 10% aqueous solution induces no irritation to skin.
Executive summary:

Undiluted Cubidow is slightly to moderately irritating to intact and abraded skin. Contact for a short period of time would probably result in no appreciable irritation. Skin contact on a prolonged basis, particularly in the case of moist or wet skin and if confined to the surface as exemplified by contaminated gloves or clothing in general, might produce some reddening. If the material were allowed to remain in contact on a continuous basis for a day or two, it is likely that a slight skin burn might result, particularly if the skin were abraded or was otherwise abnormal as exemplified by skin rashes, etc.

However to intact skin, very slight or slight irritation were seen with pur substance. No irritation was induced with a10% aqueous solution.

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:
weight of evidence
Study period:
1954
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data is available for interpretation of results.
Qualifier:
no guideline available
Principles of method if other than guideline:
None
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
water
Remarks:
for 5%, 10%, 20% and 50 % NaCl solution
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Concentration (if solution): 5%, 10%, 20% and 50 % and 100% NaCl
Duration of treatment / exposure:
No data
Observation period (in vivo):
No data
Number of animals or in vitro replicates:
No data
Details on study design:
Please see the table below.
Remarks on result:
other: Based on observations, the substance can be considered as irritating for eyes. No scores are available on this study.
Remarks:
The following responses were observed: pain, conjunctival irritation and corneal injury.
Irritant / corrosive response data:
Sodium chloride and its strong solution (50%) present a slight hazard from contact with the eye. Pain and conjunctival inflammation may persist for several days. Transient corneal injury may occur, but is expected to heal completely within a few days. Solution (20% or less) are not likely to cause injury to the eye. Contact is but very slightly painful and irritating.
Other effects:
None

None

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Sodium chloride presents a hazard from eye contact, both in the solid form and at the 50% concentration in water. Lower concentration (20% and 10%) cause slight pain and irritation which heals readily. Solutions of 5% cause only a trace of pain and no irritation.
Executive summary:

Sodium chloride or its concentrated solutions (50% or greater) caused pain and conjunctival inflammation which persisted for several days. Transient corneal injury occurred which resolved completely within a few days. Solutions of 20% or less caused slight pain and irritation which healed readily. Solutions of 5% or less caused only a trace of pain and no irritation.

Pure substance and 50% in solution is considered to induce eye irritation. Solution of 20% or less induces only slight eye irritation.

As a comparative reference, normal seawater is ~3.3% salt solution.

Only pure substance and solution of 50% are considered to be irritating to eyes and are classified Eye. irrit. Cat. 2, H319 according to EU GHS criteria.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1960
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines.
Qualifier:
no guideline available
Principles of method if other than guideline:
None
GLP compliance:
no
Species:
rabbit
Strain:
not specified
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
Test substance was applied undiluted as well as 10% aqueous solution.
Duration of treatment / exposure:
Single
Observation period (in vivo):
One week
Number of animals or in vitro replicates:
No data
Details on study design:
Please see the table below
Irritation parameter:
other: see remarks
Remarks:
The following responses were observed: pain, conjunctival irritation and corneal injury.
Basis:
other: see remarks
Remarks:
Not specified
Time point:
other: not specified
Reversibility:
fully reversible within: see remarks
Remarks:
one weeks.
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
Slight pain and conjunctivitis were observed when cubidow (Sodium chloride) was administered undiluted. 10% aqueous solution showed slight conjunctivitis.
Other effects:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
The undiluted cubidow is only slightly irritating to the eyes.
Executive summary:

The undiluted Cubidow (Sodium chloride) is only slightly irritating to the eyes. Direct contact produced slight swelling accompanied by slight reddening, but appreciable corneal injury was not observed. The 10% solution was somewhat less irritating than the undiluted material.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Sufficient information is available for interpretation of results.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
None
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
No data
Vehicle:
water
Controls:
not specified
Amount / concentration applied:
0.01, 0.05 and 0.1 ml Nacl (20% or granular)
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
1, 2, 3, 4, 7 and 14 days after dosing
Number of animals or in vitro replicates:
3
Details on study design:
Young adult New Zealand albino rabbits of both sexes were selected at random and accepted for testing if free of visible ocular lesions when examined under good illumination with the aid of a magnifying lens. The lids of the test eyes were gently held open and the test material placed directly on the cornea. Only one eye of each animal was used in a test; the other eye being untreated served as a control. Liquid doses were dispensed from a micropipette, solids from a weighing paper. The eyelids were released immediately and not forcibly closed or further manipulated. The eye was not irrigated.

Eyes were examined and scored according to the scale of Draize et al. (1944) 1, 3, 7, and 14 days.
Three eyes were dosed with granular and 20% aqueous sodium chloride using volumes of 0.1, 0.01 and 0.05 ml.
Irritation parameter:
overall irritation score
Remarks:
Maximum draize score
Basis:
mean
Time point:
other: not specified
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 1 day
Remarks on result:
other: 0 ± 0, for Sodium chloride (20%) - 0.01 ml
Irritation parameter:
overall irritation score
Remarks:
Maximum Draize score
Basis:
mean
Time point:
other: not specified
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 1 day
Remarks on result:
other: 0 ± 0, for Sodim chloride (20%) - 0.05 ml
Irritation parameter:
overall irritation score
Remarks:
Maximum Draize score
Basis:
mean
Time point:
other: not specified
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 1 day
Remarks on result:
other: 0 ± 0, for Sodium chloride (20%) - 0.10 ml
Irritation parameter:
overall irritation score
Remarks:
Maximum Draize score
Basis:
mean
Time point:
other: not specified
Score:
9
Max. score:
9
Reversibility:
fully reversible within: 3-4 days
Remarks on result:
other: 9 ± 1, for Sodium chloride (granular) - 0.01 mg
Irritation parameter:
overall irritation score
Remarks:
Maximum Draize score
Basis:
mean
Time point:
other: not specified
Score:
11
Max. score:
11
Reversibility:
fully reversible within: 4-7 days
Remarks on result:
other: 11 ± 1, for Sodium chloride (granular) - 0.05 mg
Irritation parameter:
overall irritation score
Remarks:
Maximum Draize score
Basis:
mean
Time point:
other: not specified
Score:
13
Max. score:
13
Reversibility:
fully reversible within: 4-7 days
Remarks on result:
other: 13 ± 1, for Sodium chloride (granular) - 0.10 mg
Irritant / corrosive response data:
20% Sodium chloride showed negligible irritation (clearing within 24 hour after dosing). Granular sodium chloride showed moderate irritation (clearing within 7 days after dosing).
Other effects:
None

Please see the attachment - Eye irritation for details on results.

Tha attachment contains:

Table 1: Preliminary study Rabbit eye irritation scores and days to clear with different dose volumes of materials.

Table 5: Criteria for a positive reaction: FHSA Rabbit eye irritation test

Table 7: Presumptive assessment of hazardousness from FHSA and Proposed evaluative criteria

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Granular Sodium Chloride is classified as moderate irritant as specified by FHSA criteia (0.01ml).
Based on the results the classification Eye irrit. Cat. H319 according to EU GHS criteria is recommended for granular sodium chloride.
Executive summary:

Young adult New Zealand albino rabbits of both sexes were selected at random and accepted for testing if free of visible ocular lesions when examined under good illumination with the aid of a magnifying lens. The lids of the test eyes were gently held open and the test material placed directly on the cornea. Only one eye of each animal was used in a test; the other eye being untreated served as a control. Liquid doses were dispensed from a micropipette, solids from a weighing paper. The eyelids were released immediately and not forcibly closed or further manipulated. The eye was not irrigated. Eyes were examined and scored according to the scale of Draize et al. (1944) 1, 3, 7, and 14 days. Three eyes were dosed with granular and 20% aqueous sodium chloride using volumes of 0.1, 0.01 and 0.05 ml.

20% Sodium chloride showed negligible irritation (clearing within 24 hour after dosing). Granular sodium chloride showed moderate irritation (clearing within 7 days after dosing).

Based on the results of the study, granular Sodium Chloride is classified as moderate irritant as specified by FHSA criteia (0.01ml). Therefore granular sodium chloride is considered to be irritating to eyes and should be classified Eye. Irrit. Cat. 2, H319 according to EU GHS criteria.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented publication, comparable to guideline but with acceptable restrictions. In the OECD SIDS on sodium carbonate (2002) a similar reliability was assigned.
Principles of method if other than guideline:
Method: Draize Test
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Strain: New Zealand albino.
- Sex: Unselected.
- Source: Zartman Farms, P.A. Animals.
- Age: Not reported.
- Weight at study initiation: 2.0-2.5 kg.
- Number of animals: 6 with washed eyes and 12 with unwashed eyes.
- Controls: Left eye.
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
Duration of treatment / exposure:
24 hour(s)
Number of animals or in vitro replicates:
18
Details on study design:
METHOD FOLLOWED: Based on the methodology of Draize et al. (1944) and the FHSAR (1973) with slight modifications. Comparable to OECD guideline 405.
DEVIATIONS FROM OECD GUIDELINE 405: The test material was placed directly on the central portion of the cornea (right eye) instead of placing it in a cup formed by the conjunctival sac. Evaluation system different.
Comment: Of six animals the eyes were washed for 2 minutes, 30 seconds after instillation. Of 12 animals the eyes were not washed.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 hr
Score:
3.8
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: unrinsed eyes
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 + 48 + 72 + 168 hr
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: unrinsed eyes
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 48 hr
Score:
0.8
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: rinsed eyes
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: rinsed eyes
AVERAGE SCORE
- Cornea: 3.1 (0.4 in unwashed eyes)
- Iris: 2.0 (0.6 in unwashed eyes)
- Conjuntivae (Redness): Not reported.
- Conjuntivae (Chemosis): Not reported.
- Overall irritation score: Not reported.
DESCRIPTION OF LESIONS: Conjunctivitis was observed in all
animals and lasted through day 7. Pannus was observed in
6/12 unwashed eyes and keratoconus in 2/12 unwashed eyes.
REVERSIBILITY: Effects were reversible in washed eyes, but
not in unwashed eyes.
OTHER EFFECTS: No.
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Executive summary:

In a study based on the methodology of Draize et al. (1944) and the FHSAR (1973) with slight modifications. Comparable to OECD guideline 405. The test material (0.1 ml) was placed directly on the central portion of the cornea (right eye) of New Zealand Albinos rabbits. For six animals the eyes were washed for 2 minutes, 30 seconds after instillation. For 12 animals the eyes were not washed. The average scores were the following: Cornea: 3.1 (0.4 in unwashed eyes) ; Iris: 2.0 (0.6 in unwashed eyes) ; Conjuntivae (Redness): Not reported ; Conjuntivae (Chemosis): Not reported ; Overall irritation score: Not reported.

Conjunctivitis was observed in all animals and lasted through day 7. Pannus was observed in 6/12 unwashed eyes and keratoconus in 2/12 unwashed eyes. Effects were reversible in washed eyes, but not in unwashed eyes.

Based on this study sodium carbonate is highly irritating for eyes and the substance is classified Eye. irrit. Cat. 2, H319 according to EU GHS criteria.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant guideline study with minor deviations, fully adequate for assessment. In the OECD SIDS on sodium carbonate (2002) a similar reliability was assigned.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
Minor deviations included housing conditions
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Sex: Not reported.
- Source: Harald Schriever, Rabbit farm, Germany.
- Age: Not reported.
- Weight at study initiation: 2.4 - 2.6 kg
- Controls: Right eye.
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
undiluted
Amount applied: 0.1 other: g
Duration of treatment / exposure:
72 hour(s)
Number of animals or in vitro replicates:
6
Details on study design:
ADMINISTRATION/EXPOSURE:
- Amount of substance instilled: 0.1 g in left eye; right eye not treated.
- Postexposure period: Up to 72 hr.
EXAMINATIONS
- Ophtalmoscopic examination: Yes.
- Scoring system: Draize scheme
- Observation period: 1, 24, 48, and 72 hr.
- Tool used to assess score: Two independent persons using grade system as described in OECD 405.
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 1 + 24 + 48 + 72 hr
Score:
0.25
Max. score:
2
Reversibility:
fully reversible
Remarks:
within 72 hr
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 1 + 24 + 48 + 72 hr
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks:
within 72 hr
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 1 + 24 + 48 + 72 hr
Score:
1.67
Max. score:
3
Reversibility:
not fully reversible within: 72 hr in one animal
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 + 24 + 48 + 72 hr
Score:
1.38
Max. score:
4
Reversibility:
not fully reversible within: 72 hr in on animal
Other effects:
DESCRIPTION OF LESIONS: Not reported.
REVERSIBILITY: All effects were reversible, only one animal showed conjunctival redness and chemosis after 72 hr (score 1), but this score was decreasing.
OTHER EFFECTS: No.
Interpretation of results:
GHS criteria not met
Executive summary:

In this study conducted according to an OECD TG 405, 0.1 gr of sodium carbonate has been instilled in the eyes of 6 New Zealand White Rabbits. The scores calculated for 1, 24, 48 and 72 hours were the following: Iris scores: 0.25 ; Cornea scores: 0 ; Conjunctivae: 1.67 and Chemosis: 1.38. Furthermore, only one animal showed conjunctival redness and chemosis after 72h. But this was decreasing and reversibility within 21 days is expected.

Based on this result sodium carbonate is not expected to be irritant for eyes. No classification is required according to EU GHS criteria.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-comparable guideline study, no restrictions, fully adequate for assessment. In the OECD SIDS on sodium carbonate (2002) a similar reliability was assigned.
Qualifier:
according to guideline
Guideline:
other: EPA 16 CFR 1500.42
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS:
- Sex: Not reported.
- Source: Marland Breeding Farms, Inc., Hewitt, NJ.
- Age: Not reported.
- Weight at study initiation: Not reported.
- Number of animals: 9.
- Controls: The test substance was not administered in one eye of each animal, this eye served as a control.
Vehicle:
unchanged (no vehicle)
Amount / concentration applied:
undiluted
Amount applied: 0.1 ml
Number of animals or in vitro replicates:
9
Details on study design:
METHOD FOLLOWED: 16 CFR 1500.42.
DEVIATIONS FROM GUIDELINE: Yes, but not reported in detail by the authors.
ADMINISTRATION/EXPOSURE:
- Amount of substance instilled: 0.1 ml.
- Vehicle: None.
- Postexposure period: The treated eyes of three rabbits were rinsed with 30 ml of distilled water, 4 seconds following compound administration. The remaining six animals received no further treatment. Animals were observed until 14 days after exposure.
EXAMINATIONS
- Ophtalmoscopic examination: The eyes were examined and scored for ocular reactions on days 1,2,3, 4,7,10 and 14 following installation of the test compound, or until the eyes were determined to be free of ocular irritation for two consecutive observations.
- Scoring system: The Draize method was employed.
- Observation period: 14 days.
- Tool used to assess score: A fluorescein wash was used when necessary in scoring ocular reactions.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: maximal score from observations at days 1, 2, 3, 4, 7, 10 and 14
Score:
105
Max. score:
110
Reversibility:
not fully reversible within: 14 days
Irritant / corrosive response data:
AVERAGE SCORE
- Cornea: According to the scoring system employed, the responses were positive (+) or negative (-). 6/6 animals with unwashed eyes had a positive score. 1/3 animals with washed eyes had a positive score.
- Iris: According to the scoring system employed, the responses were positive (+) or negative (-). 6/6 animals with unwashed eyes had a positive score. 1/3 animals with washed eyes had a positive score.
- Conjuntivae (Redness): According to the scoring system employed, the responses were positive (+) or negative (-). 6/6 animals with unwashed eyes had a positive score. 1/3 animals with washed eyes had a positive score.
- Conjuntivae (Chemosis): According to the scoring system employed, the responses were positive (+) or negative (-). 6/6 animals with unwashed eyes had a positive score. 1/3 animals with washed eyes had a positive score. The incidence of necrosis or ulceration was also registered. 6/6 animals with unwashed eyes had a positive score, and 2/3 animals with washed eyes had a positive score.
- Overall irritation score: The maximum Draize scores in the animals with unwashed eyes were: 88, 108, 104,110, 110, 108; the mean was 105. The maximum Draize scores in the animals with washed eyes were: 30, 6, 4; the mean was 13.
DESCRIPTION OF LESIONS: All six unwashed eyes were assigned positive scores for corneal opacity. Five eyes were assigned positive scores for ulceration. Pannus was observed in the 4 intact eyes beginning on day 7 of the study (2 eyes ruptured on day 7). Iritis was evident in all six eyes. Each unwashed eye had conjunctival redness, chemosis and necrosis/ulceration. Alopecia was observed around 1 treated eye. Bleeding was noted on one eyelid while the eyelids of two different eyes were observed to be healing closed by day 14. Signs of irritation were evident in the four intact unwashed eyes at the termination of the study. Corneal opacity and ulceration were observed in one of three eyes washed at 4 seconds. One eye was assigned positive scores for conjunctival redness and chemosis, and 2 eyes were assigned positive scores for conjunctival ulceration. Signs of irritation were evident in one eye at the termination of the study. REVERSIBILITY: Among the animals with unwashed eyes, 2 suffered ruptured eyes and the remaining 4 still had signs of irritation at the termination of the study. One of the animals with washed eyes had signs of irritation at the termination of the study, while the eye appeared normal in the remaining two animals on day 2 and 14, respectively.
Other effects:
Not reported.
AVERAGE SCORE 
- Cornea: According to the scoring system employed, the responses were positive (+) or negative (-).  6/6 animals with unwashed eyes had a positive score. 1/3 animals with washed eyes had a positive score. 
- Iris: According to the scoring system employed, the responses were positive (+) or negative (-).  6/6 animals with unwashed eyes had a positive score. 1/3 animals with washed eyes had a positive score. 
- Conjuntivae (Redness): According to the scoring system employed, the responses were positive (+) or negative (-).  6/6 animals with unwashed eyes had a positive score. 1/3 animals with washed eyes had a positive score. 
- Conjuntivae (Chemosis): According to the scoring system employed, the responses were positive (+) or negative (-).  6/6 animals with unwashed eyes had a positive score. 1/3 animals with washed eyes had a positive score. The incidence of necrosis or ulceration was also registered.  6/6 animals with unwashed eyes had a positive score, and 2/3 animals with washed eyes had a positive score. 
- Overall irritation score: The maximum Draize scores in the animals with unwashed eyes were: 88, 108, 104,110, 110, 108; the mean was 105. The maximum Draize scores in the animals with washed eyes were: 30, 6, 4; the mean was 13.  
DESCRIPTION OF LESIONS: All six unwashed eyes were assigned positive scores for corneal opacity.  Five eyes were assigned positive scores for ulceration. Pannus was observed in the 4 intact eyes beginning on day 7 of the study (2 eyes ruptured on day 7). Iritis was evident in all six eyes. Each unwashed eye had conjunctival redness, chemosis and necrosis/ulceration. Alopecia was observed around 1 treated eye.  Bleeding was noted on one eyelid while the eyelids of two different eyes were observed to be healing closed by day 14. Signs of irritation were evident in the four intact unwashed eyes at the termination of the study. Corneal opacity and ulceration were observed in one of three eyes washed at 4 seconds. One eye was assigned positive scores for conjunctival redness and chemosis, and 2 eyes were assigned positive scores for conjunctival ulceration. Signs of irritation were evident in one eye at the termination of the study. REVERSIBILITY: Among the animals with unwashed eyes, 2 suffered ruptured eyes and the remaining 4 still had signs of irritation at the termination of the study.  One of the animals with washed eyes had signs of irritation at the termination of the study, while the eye appeared normal in the remaining two animals on day 2 and 14, respectively.
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Executive summary:

In this study, 0.1 ml of sodium carbonate has been applied in the eyes of 9 New Zealand White rabbits. The eyes were either rinsed 4 seconds after instillation or not rinsed during the test period. All six unwashed eyes were assigned positive scores for corneal opacity.  Five eyes were assigned positive scores for ulceration. Pannus was observed in the 4 intact eyes beginning on day 7 of the study (2 eyes ruptured on day 7). Iritis was evident in all six eyes. Each unwashed eye had conjunctival redness, chemosis and necrosis/ulceration. Alopecia was observed around 1 treated eye. Based on these results sodium carbonate is considered as irritating for eye and is classified Eye. irrit. cat. 2, H319 according to EU GHS criteria.

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Cited as Directive 84/449/EEC, B.5
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS: Rabbits
- Strain: HC:NZW 
- Sex: not described
- Source: Interfauna, Ltd, UK
- Age: adults
- Weight at study initiation: not described 
- Number of animals: 3
- Controls: other eye
Vehicle:
not specified
Amount / concentration applied:
Concentration: 90 mg
Amount applied: 100 µl

- Preparation of test substance: Pulverized powder
- Vehicle: not described
Duration of treatment / exposure:
24 hour(s)
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
3
Details on study design:
- exposure : 24 hours

EXAMINATIONS
- Ophtalmoscopic examination: yes
- Scoring system: DRAIZE system
- Observation period: 21 days
- Tool used to assess score: optical instrument (hand slit lamp)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
no indication of irritation
Interpretation of results:
GHS criteria not met
Conclusions:
Classification: not irritating
Executive summary:

In a study performed according to the EU method B.5, 90 g of sodium sulfate have been instillated in eyes of rabbit. Theeyes were observed until 21 days. The scores are the following: Cornea: 0; Iris: 0; Conjuntivae: 1 ; Chemosis: 0. Based on this result, sodium sulfate in not classified irritating to eyes according to EU GHS criteria.

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
See Read-across justification attached.
No data are available on the reaction mass itself. Data on the three components of the reaction mass are used. Sodium carbonate is more toxic than sodium chloride and sodium sufate regarding eye irritation. Therefore only score on sodium carbonate are reported and since sodium carbonate is classified Eye. Irrit. cat. 2, H319, this classification is also proposed for the reaction imass tself.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
72 h
Score:
3.8
Reversibility:
not fully reversible within:
Remarks on result:
other: unrinsed eye
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
2
Reversibility:
not fully reversible within:
Remarks on result:
other: unrinsed eye
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Taken into account the three components and based on the data of sodium carbonate (the more toxic component regarding eye irritation) the reaction mass is considered irritating for eyes and is classified Eye. Irrit. Cat. 2, H319 according to EU GHS criteria.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Justification for classification or non-classification

Skin irritation:

Three unpublished reports with reliability 2 are available on sodium chloride. In the first one (Indust. bio test 1961), sodium chloride moistened with water induced slight irritation to rabbit skin. In the second report (Dow, 1960), no irritation was observed in rabbit skin (sodium chloride in solution and pure sodium chloride). Based on the third study (Dow, 1954), undiluted sodium chloride induces very slight to slight irritations. 10% aqueous solution induced no skin irritation in rabbit. Furthermore, Sodium chloride is used as a food additive and based on human experience it can be concluded that this substance is not irritating to the skin.

Sodium carbonate is included in Annex VI of the CLP Regulation but it is not labelled for skin irritation and in several reliable studies no irritation was observed in rabbit skin and on human skin (OECD SIDS).

In one reliable study (Bayer 1988, Klimisch 1), sodium sulfate is not irritating to the skin.

Overall it can be concluded that the reaction mass (a solution of these salts in water) is not irritating to the skin because the constituents are not irritating to the skin.  

Based on the data on all components of the reaction mass, no classification for skin irritation is required according to UN and EU GHS criteria.

Eye irritation:

Three studies are available on sodium chloride showing that sodium chloride induced pain to eyes rabbits. In a conservative approach sodium chloride is considered to be irritating to eyes.

For the sodium sulfate, one reliable OECD 405 study showed a slightly irritation of eye due to its slight effect on conjunctivae.

For the sodium carbonate, three reliable studies are available. One of them (Murphy’s et al., 1982) shown a high irritation. Furthermore, sodium carbonate is officially classified (Index number : 011-005-00-2) on table 3 of Annex VI of EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 as Eye . Irrit. Category 2, H319.

In a worst case approach considering the data on sodium chloride and on sodium carbonate, the reaction mass (Sodium chloride, sodium carbonate and sodium sulfate) can induce irritation to eyes and is classified Eye. Irrit. Cat. 2, H319.