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Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Draize scoring system slightly modified, but with no effect on the results. - Test procedure, housing conditions, purity and stability were missing in the report. - Overall, the study is still good enough documented in order to use the study for RA.
Justification for type of information:
The basis for the read-across concept for this project is the equilibrium between sulfites, hydrogensulfites, and metabisulfites in aqueous solutions depending on pHvalue which is clearly described in published literature and summarised in the following equations:[1],[2]
           SO2+ H2O <->`H2SO3´         H2SO3<->H++ HSO3-<->2H++SO32-    2HSO3-<->H2O +S2O52 -
As the nature of the cation should make no significant difference in this case concerning toxicity and solubility (all compounds are very soluble in water), only the chemical and biological properties of the anion are considered relevant. Based on the described equilibrium correlations, we propose unrestricted read-across between the groups of sulfites, hydrogensulfites and metabisulfites.

Additionally, it is known that sodium dithionite disproportionates in water to form sodium hydrogen sulfite and sodium thiosulfate (equation II) so that this substance can also be added to the read-across concept.[2],[1]It is expected for this case that the substance is not stable enough under physiological conditions to fulfil the requirements of study guidelines and so the products of decomposition have to be considered.
       2 S2O42-+ H2O→2HSO3-+ S2O32 -
 
Not completely included in this read-across concept is the substance class of thiosulfates. Although thiosulfates may also disproportionate in aqueous solution to form polythionic acids and SO2(HSO3-), the required conditions are somewhat different (more acidic) and are therefore not strictly comparable with physiological conditions, except for the case of oral application where read-across should be considered unrestricted due to the strongly acidic conditions in the stomach:
       HS2O3-+ H2S2O3→HS3O3- + SO2 + H2O
Nevertheless, read-across for all other routes (dermal, inhalation) should also be considered.
The proposed read-across concept only applies to toxicological and ecotoxicological/environmental fate endpoints.
[1]Hollemann Wiberg, Lehrbuch der Anorganischen Chemie, 101.Auflage
[2]Handbook of Chemistry and Physics, Ed. Lide, DR, 88thedition, CRC Press

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
, see "Rationale for reliability" above
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium sulphite
EC Number:
231-821-4
EC Name:
Sodium sulphite
Cas Number:
7757-83-7
Molecular formula:
NA2SO3
IUPAC Name:
disodium sulfite
Test material form:
solid
Details on test material:
- Name of test material (as cited in study report): Natriumsulfit aktiviert wasserfrei
- Chemical description: Sodium sulfit + 0.5% cobalt sulfate
- Molecular formula: Na2SO3 + 0.5% CoSO4 * 7H2O
- Physical state: Solid

Test animals / tissue source

Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Gaukler
- Weight at study initiation: Mean body weight of male rabbits: 2.78 kg; mean body weight of female rabbits = 3.36 kg
- Diet (e.g. ad libitum): SSNIFF of the company Intermast
no furthre information on the test animals was stated.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 162 mg of test item (equivalent to 0.1 ml bulk volume)
No further information on the amount/concentration applied was stated.
Duration of treatment / exposure:
No data
Observation period (in vivo):
Readings: 1 h, 24 h, 48 h, 72 h, 8 d after application
Number of animals or in vitro replicates:
Total: 6 rabbits (2 males/ 4 females)
Details on study design:
SCORING SYSTEM:
-Assessment: Modified Draize scoring system
Cornea/chemosis:
0 = not observed
1 = slight
2 = clear
3 = heavy
4 = very heavy
Conjunctival redness:
0 = normal
1 = slight intensified
2 = clear
3 = heavy
Iris:
1 = ciliar injection
2 = iritis
Area of opacity:
1 = > 0; < 1/4
2 = ≥ 1/4; < 1/2
3 = ≥ 1/2; < 3/4
4 = ≥ 3/4

Secretion:
0 = normal
1 = slightly increased
2 = clearly increased
3 = heavily increased

TOOL USED TO ASSESS SCORE: Fluorescein was used at the reading on Day 8 after application
No further information on the study design was stated.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
Animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #11
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: At 24 hours blood was observed.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Slight conjunctival redness was again observed on Day 8.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
other: At 24 hours blood was observed
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight conjunctival redness was again observed on Day 8
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #4
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #5
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #5
Time point:
24/48/72 h
Score:
1
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #6
Time point:
24/48/72 h
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #6
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
The following observations wer made during the 1-hour observation:
Animal #1: Clear conjunctival redness and chemosis (Score 2); slight secretion; blood was seen
Animal #2: Clear conjunctival redness and chemosis (Score 2); clearly secretion; blood was seen
Animal #3: Clear conjunctival redness and chemosis (Score 2); slight secretion
Animal #4: Clear conjunctival redness and chemosis (Score 2); clearly secretion; blood was seen
Animal #5: Clear conjunctival redness (Score 2) and heavy chemosis; clearly secretion; blood was seen
Animal #6: Slight conjunctival redness (Score 1) and chemosis (Score 2); clearly secretion

Any other information on results incl. tables

Overall irritation/corrosion results:

Irritation parameter

Basis

Time point

Score

Max. score

Reversibility

 Remarks

Cornea score

Mean animal #1

24, 48, and 72 hours

0

4

 

 

Iris score

Mean animal #1

24, 48, and 72 hours

0

2

 

 

Conjunctivae score

Mean animal #1

24, 48, and 72 hours

1.67

3

fully reversible within:

8 days

 

Chemosis score

Mean animal #1

24, 48, and 72 hours

0.33

4

fully reversible within:

48 hours

 

Cornea score

Mean animal #2

24, 48, and 72 hours

0

4

 

At 24 hours blood was observed.

Iris score

Mean animal #2

24, 48, and 72 hours

0

2

 

 

Conjunctivae score

Mean animal #2

24, 48, and 72 hours

0.67

3

fully reversible within:

48 hours

 

Chemosis score

Mean animal #2

24, 48, and 72 hours

0.67

4

fully reversible within:

48 hours

 

Cornea score

Mean animal #3

24, 48, and 72 hours

0

4

 

 

Iris score

Mean animal #3

24, 48, and 72 hours

0

2

 

 

Conjunctivae score

Mean animal #3

24, 48, and 72 hours

0.33

3

fully reversible within:

48 hours

Slight conjunctival redness was again observed on Day 8.

Chemosis score

Mean animal #3

24, 48, and 72 hours

0

4

 

 

Cornea score

Mean animal #4

24, 48, and 72 hours

0

4

 

At 24 hours blood was observed.

Iris score

Mean animal #4

24, 48, and 72 hours

0

2

 

 

Conjunctivae score

Mean animal #4

24, 48, and 72 hours

1.33

3

fully reversible within:

72 hours

Slight conjunctival redness was again observed on Day 8.

Chemosis score

Mean animal #4

24, 48, and 72 hours

0.33

4

fully reversible within:

48 hours

 

Cornea score

Mean animal #5

24, 48, and 72 hours

0

4

 

 

Iris score

Mean animal #5

24, 48, and 72 hours

0

2

 

 

Conjunctivae score

Mean animal #5

24, 48, and 72 hours

1.33

3

 

 

Chemosis score

Mean animal #5

24, 48, and 72 hours

1

4

 

 

Cornea score

Mean animal #6

24, 48, and 72 hours

0

4

 

 

Iris score

Mean animal #6

24, 48, and 72 hours

0

2

 

 

Conjunctivae score

Mean animal #6

24, 48, and 72 hours

0.33

3

fully reversible within:

48 hours

 

Chemosis score

Mean animal #6

24, 48, and 72 hours

0.67

4

fully reversible within:

48 hours

 

Animal   1  2  3  4  5  6
 Animal No.  0163  0162  0185  0159  0841  014
 Animal weight (kg)  3.44  3.47  3.49  3.02  3.16  2.40
 Sex  female  female  female  female  male  male
 Readings  Animal  Cornea     Iris  Conjunctivae        Signs
 Opacity  Area  Redness  Swelling  Discharge
24 hours   1 0 0 0 2 1 2  
 2 0 0 0 2 2 2  
 3 0 0 0 1 0 0  
 4 0 0 0 2 1 1  Scar
 5 0 0 0 1 2 1  
 6 0 0 0 1 2 2  
 48 hours  1 0 0 0 2 0 0  
 2 0 0 0 0 0 0  
 3 0 0 0 0 0 0  
 4 0 0 0 2 0 0  Scar
 5 0 0 0 2 1 1  
 6 0 0 0 0 0 0  
 72 hours  1 0 0 0 1 0 0  
 2 0 0 0 0 0 0  
 3 0 0 0 0 0 0  
 4 0 0 0 0 0 0  Scar
 5 0 0 0 1 0 0  
 6 0 0 0 0 0 0  
 8 days  1 0 0 0 0 0 0  
 2 0 0 0 0 0 0  
 3 0 0 0 1 0 0  
 4 0 0 0 1 0 0  Scar
 5 0 0 0 0 0 0  
 6 0 0 0 0 0 0  
mean 24 - 72 h  1 0.0 0.0 0.0 1.7 0.3 0.7  
 2 0.0 0.0 0.0 0.7 0.7 0.7  
 3 0.0 0.0 0.0 0.3 0.0 0.0  
 4 0.0 0.0 0.0 1.3 0.3 0.3  
 5 0.0 0.0 0.0 1.3 1.0 0.7  
 6 0.0 0.0 0.0 0.3 0.7 0.7  
mean   0.0 0.0 0.0 0.9 0.5 0.5  

Conjunctivae

Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris) - Vessels normal 0 - Vessels definitely injected above normal 1 - More diffuse, deeper crimson red, individual vessels not easily discernible 2

Chemosis - No swelling 0 - Any swelling above normal (includes nictitating memnbrane) 1 - Obvious swelling with partial eversion of lids 2

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Sodium sulphite is not an eye irritant.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as eye irritant.

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