Registration Dossier

Administrative data

Description of key information

Skin irritation in vivo: 1,3,4-thiadiazole-2,5-dithiol undiluted, CFR Section 1500.41, albino rabbits, 24h occlusive: not irritating

Skin irritation in vivo: 30% disodium 1,3,4-thiadiazole-2,5-dithiolate in water, CFR Section 1500.41, albino rabbits, 24h occlusive: not irritating

Eye irritation in vivo: 1,3,4-thiadiazole-2,5-dithiol undiluted, CFR Section 1500.42, albino rabbits, no wash-out: severe ocular irritant, Eye Dam. Cat. 1

Eye irritation in vivo: 30% disodium 1,3,4-thiadiazole-2,5-dithiolate in water, CFR Section 1500.42, albino rabbits, no wash-out: not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Remarks:
In vivo study performed prior (1980) to REACH implementation.
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1980-09-30 - 1980-10-03 (experimental phase)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Given information allows the conclusion the study was well performed according to adopted guidelines, given data allows also conclusions on classification according to Regulation 1272/2008.
Qualifier:
according to
Guideline:
other: CFR Section 1500.41
Version / remarks:
The method employed in the testing, evaluation and the scoring of the results was similar to that described in Section 1500.41 ― Federal Hazardous Substances Act Regulations ― 16 CFR - P. 124,
Deviations:
not specified
GLP compliance:
no
Species:
rabbit
Strain:
other: Albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR Part 3.
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact (clipped only)
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g
Duration of treatment / exposure:
24h occlusive under Wrap. no wash-off
Observation period:
72h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: A 0.5 g portion of material was applied to an abraded and an intact skin site on the same rabbit.
- Type of wrap if used: Gauze patches were then placed over the treated areas and an impervious material was wrapped snugly around the trunks of the animals to hold the patches in place.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none washing stated

OBSERVATION TIME POINTS
after 24 and 72 hours

SCORING SYSTEM:
- Method of calculation: The Draize method of scoring was employed. Scoring of the results was similar to that described in Section 1500.41 ― Federal Hazardous Substances Act Regulations ― 16 CFR - P. 124.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24&72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24&72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24&72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Remarks:
Information on the 48h timepoint not given, but as after 24h and 72h the score in each animal is zero, it can be concluded that this is the case also after 48h.
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Remarks:
Information on the 48h timepoint not given, but as after 24h and 72h the score in each animal is zero, it can be concluded that this is the case also after 48h.
Irritant / corrosive response data:
not irritant
Other effects:
- Other adverse local effects: none stated
- Other adverse systemic effects: none stated
Interpretation of results:
GHS criteria not met
Conclusions:
Study was performed scientifically reasonable similar to that described in Section 1500.41 ― Federal Hazardous Substances Act Regulations ― 16 CFR - P. 124 on 1,3,4-Thiadiazole-2,5-dithiole, and is sufficiently documented. Hence, the results can be considered as reliable to assess the irritating potential of 1,3,4-Thiadiazole-2,5-dithiole on intact and abraded rabbit skin. The primary irritation score was 0.00, none of the 6 rabbits showed any sign of irritation. Hence, the substance does not need to be classified as skin irritant acc. Regulation 1272/2008.
Executive summary:

In a primary dermal irritation study (16 CFR Section 1500.41), six Albino rabbits were dermally exposed to each 0.5 g of unchanged 1,3,4-Thiadiazole-2,5-dithiole for 24 hours to intact and abraded skin, no washing.  Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

The primary irritation score was 0.00, none of the 6 rabbits showed any sign of irritation. The substance does not need to be classified as skin irritant acc. Regulation 1272/2008.

Endpoint:
skin irritation: in vivo
Remarks:
In vivo study performed prior (1980) to REACH implementation.
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1980-09-19 - 1980-10-03 (experimental phase)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Given information allows the conclusion the study was well performed according to adopted guidelines, given data allows also conclusions on classification according to Regulation 1272/2008, read-across
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The rational for the analogue approach is the high structural similarity between the source and the target substance. The source chemical is the disodium salt of the registered substance. The organic structure hence is identical, the only difference is the ionisation of the nitrogen with sodium as counterions compared to the hydrogen bound to the nitrogen of the target (registered) substance. Further, when brought into acidic environment, a at least partial ionisation can be expected. Hence, data on disodium 1,3,4-thiadiazole-2,5-dithiolate can be used to sufficiently prove that the results gained on 1,3,4-thiadiazole-2,5-dithiol itself serve as a worst case for hazard assessment. Due to the similarities in structure, similar physico-chemical properties of the substances are to be expected, which would result in a similar toxicokinetic behaviour and most likely also in very similar toxicodynamic and toxicological behaviour.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical: disodium 1,3,4-thiadiazole-2,5-dithiolate, CAS 55906-42-8, SMILES Code [Na+].[Na+].S=C1[N-][N-]C(=S)S1, MW = 194.2 g/mol
Target chemical: 1,3,4-thiadiazole-2,5-dithiol, CAS 1072-71-5, SMILES Code S=C1N=NC(=S)S1, MW = 150.2 g/mol

3. ANALOGUE APPROACH JUSTIFICATION
It is aimed to use data on disodium 1,3,4-thiadiazole-2,5-dithiolate to sufficiently prove that the results gained on 1,3,4-thiadiazole-2,5-dithiol itself are reliable, serve as a worst case for hazard assessment, no hence not underestimate a potential hazard and no further testing is required. As indicated under point 4 Data Matrix, both substances are small molecules with a negative estimated logPow and a high water solubility, indicating a similar absorption and distribution pattern in the body. Both substances are not irritating to the skin, which was not only shown in a dermal irritation study but further also for CAS 1072-71-5 in a skin sensitization study, which was also negative. Due to the similar behaviour on the skin, it can be concluded that CAS 55906-42-8 would also have been tested negative as a skin sensitizer, and the present study on the target substance CAS 1072-71-5 suffices for hazard assessment. CAS 1072-71-5 should be classified as acute tox. oral Cat. 4, whereas the RA substance CAS 55906-42-8 does not need to be classified, clearly showing that the available study on the registered substance itself does not underestimate a possible hazard. Similar applies to eye irritation, CAS 1072-71-5 must be classified as eye dam. Cat. 1, CAS 55906-42-8 does not.

4. DATA MATRIX
The following table shows the available data relevant to justify the read-across from the source to the target chemical to demonstrate that the available studies on the registered substance itself do not underestimate a possible hazard for the endpoints acute toxicity oral, skin and eye irritation, and skin sensitization:

Endpoint Source: CAS 55906-42-8 Target: CAS 1072-71-5
Molecular weight 194.2 g/mol 150.2 g/mol
Physical state solid solid
Partition coefficient logPow = -2.3734 (EpiSuite estimation) logPow = -0.6349 (EpiSuite estimation)
Water solubility 1e+006 mg/L 2.638e+005 mg/L
Acute toxicity oral LD50 = 2955 mg/kg (rat) LD50 = 930 mg/kg (rat)
Skin irritation Not irritating (in vivo, rabbit) Not irritating (in vivo, rabbit)
Eye irritation Not irritating (in vivo, rabbit) Eye Dam. Cat. 1 (in vivo, rabbit)
Skin sensitization n/a Not sensitizing, not a skin irritant
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: CFR Section 1500.41
Version / remarks:
The method employed in the testing, evaluation and the scoring of the results was similar to that described in Section 1500.41 ― Federal Hazardous Substances Act Regulations ― 16 CFR - P. 124,
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Albino
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR Part 3.
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact (clipped only)
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
24h occlusive under Wrap. no wash-off
Observation period:
72h
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: A 0.5 ml portion of material was applied to an abraded and an intact skin site on the same rabbit.
- Type of wrap if used: Gauze patches were then placed over the treated areas and an impervious material was wrapped snugly around the trunks of the animals to hold the patches in place.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none washing stated

OBSERVATION TIME POINTS
after 24 and 72 hours

SCORING SYSTEM:
- Method of calculation: The Draize method of scoring was employed. Scoring of the results was similar to that described in Section 1500.41 ― Federal Hazardous Substances Act Regulations ― 16 CFR - P. 124.
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24&72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24&72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24&72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Remarks:
Information on the 48h timepoint not given, but as after 24h and 72h the score in each animal is zero, it can be concluded that this is the case also after 48h.
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Remarks:
Information on the 48h timepoint not given, but as after 24h and 72h the score in each animal is zero, it can be concluded that this is the case also after 48h.
Irritant / corrosive response data:
not irritant
Other effects:
- Other adverse local effects: none stated
- Other adverse systemic effects: none stated
Interpretation of results:
GHS criteria not met
Conclusions:
Study was performed scientifically reasonable similar to that described in Section 1500.41 ― Federal Hazardous Substances Act Regulations ― 16 CFR - P. 124 on a 30% aqueous solution of disodium 1,3,4-thiadiazole-2,5-dithiolate, and is sufficiently documented. Hence, the results can be considered as reliable to assess the irritating potential of disodium 1,3,4-thiadiazole-2,5-dithiolate on intact and abraded rabbit skin. The primary irritation score was 0.00, none of the 6 rabbits showed any sign of irritation. Hence, the substance does not need to be classified as skin irritant acc. Regulation 1272/2008.
Executive summary:

In a primary dermal irritation study (16 CFR Section 1500.41), six Albino rabbits were dermally exposed to each 0.5 ml of a 30% aqueous solution of disodium 1,3,4-thiadiazole-2,5-dithiolate for 24 hours to intact and abraded skin, no washing.  Animals then were observed for 3 days.  Irritation was scored by the method of Draize.

The primary irritation score was 0.00, none of the 6 rabbits showed any sign of irritation. The substance does not need to be classified as skin irritant acc. Regulation 1272/2008

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
Remarks:
In vivo study performed prior (1980) to REACH implementation.
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1980-09-29 - 1980-10-20 (experimental phase)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Given information allows the conclusion the study was well performed according to adopted guidelines, given data allows also conclusions on classification according to Regulation 1272/2008.
Qualifier:
according to
Guideline:
other: 16 CFR Section 1500.42
Version / remarks:
The methods employed in the testing, evaluation and in the grading of the test material are similar to those described in Section 1500.42 - Federal Hazardous Substances Act Regulation CFR 16 P. 125.
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: young adult
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94--279) 9 CFR Part 3.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
The first six rabbits did not have their eyes washed subsequent to instillation. The remaining three rabbits had the treated eyes washed after 30 seconds for 1 minute with tepid water (rate of flow approximately 1000 ml/minute).
Observation period (in vivo):
The treated eyes were examined at one, two, three, five, seven, fourteen and twenty-one days following instillation and washout of the test material into the eyes.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The first six rabbits did not have their eyes washed subsequent to instillation. The remaining three rabbits had the treated eyes washed after 30 seconds for 1 minute with tepid water (rate of flow approximately 1000 ml/minute).

SCORING SYSTEM: Interpretation of the results was made in accordance with the Draize Scale of Scoring Ocular Lesions.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
3.55
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
1.89
Max. score:
2
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
2.45
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
3.22
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Remarks on result:
probability of severe irritation
Irritant / corrosive response data:
Based on the accompanying tables, the subject material is a primary ocular irritant within the definition of the Act-Reference: Section 1500.42 (b)(1)(2) and requires cautionary labelling with respect to that section.
The material is a severe ocular irritant in the unwashed eye. Washing reduces the degree and duration of the irritation substantially.
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Study was performed scientifically reasonable similar to that described in Section 1500.42 ― Federal Hazardous Substances Act Regulations ― 16 CFR - P. 125 on 1,3,4-Thiadiazole-2,5-dithiole, and is sufficiently documented. Hence, the results can be considered as reliable to assess the irritating potential of 1,3,4-Thiadiazole-2,5-dithiole on the rabbit eye in vivo.
According to Regulation 1272/2008, classification as Irreversible effects on the eye/serious damage to eyes (Category 1), If, when applied to the eye of an animal, a substance produces:
— at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/or
— at least in 2 of 3 tested animals, a positive response of:
— corneal opacity ≥ 3 and/or
— iritis > 1,5
calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.
Further, these observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test, and lesions are not fully reversible within a 21-day observation period.
An OECD 405 guideline study suffices for classification, and according to the guideline, a substance shall not be removed for 24h, solids not until 1 hour after application unless corrosion effects are noted. Hence, the results gained with animals No 7-9 cannot be used for classification, as the substance was washed out after 30 seconds. So classification must be based on the results obtained from animals No 1-6 as here the substance was not washed out. In all six animals a corneal opacity score of 4 was observed in at least one time point, all observed effects were not fully reversible after 21 days, mean corneal opacity was ≥ 3 in 5/6 animals, and iritis was also > 1,5 in 5/6 animals. Hence, the substance must be classified as Eye dam. Cat. 1.
Executive summary:

In a primary eye irritation study (16 CFR Section 1500.41), 0.1 g unchanged 1,3,4-Thiadiazole-2,5-dithiole was instilled into the conjunctival sac of the right eye of young albino rabbits. In six rabbits, the eye was not washed out, in 3 the eye was rinsed after 30 seconds. Animals then were observed for 21days.  Irritation was scored by the method of Draize.

In all six animals a corneal opacity score of 4 was observed in at least one time point, all observed effects were not fully reversible after 21 days, mean corneal opacity was ≥ 3 in 5/6 animals, and iritis was also > 1,5 in 5/6 animals. The material is a severe ocular irritant in the unwashed eye. Washing reduces the degree and duration of the irritation substantially.

In this study, 1,3,4-Thiadiazole-2,5-dithiole is severely irritating to the eye, and must be classified as Eye Dam. Cat. 1 based on the criteria of Regulation 1272/2008.

Endpoint:
eye irritation: in vivo
Remarks:
In vivo study performed prior (1980) to REACH implementation.
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1980-09-29 - 1980-10-06 (experimental phase)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Given information allows the conclusion the study was well performed according to adopted guidelines, given data allows also conclusions on classification according to Regulation 1272/2008.
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The rational for the analogue approach is the high structural similarity between the source and the target substance. The source chemical is the disodium salt of the registered substance. The organic structure hence is identical, the only difference is the ionisation of the nitrogen with sodium as counterions compared to the hydrogen bound to the nitrogen of the target (registered) substance. Further, when brought into acidic environment, a at least partial ionisation can be expected. Hence, data on disodium 1,3,4-thiadiazole-2,5-dithiolate can be used to sufficiently prove that the results gained on 1,3,4-thiadiazole-2,5-dithiol itself serve as a worst case for hazard assessment. Due to the similarities in structure, similar physico-chemical properties of the substances are to be expected, which would result in a similar toxicokinetic behaviour and most likely also in very similar toxicodynamic and toxicological behaviour.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical: disodium 1,3,4-thiadiazole-2,5-dithiolate, CAS 55906-42-8, SMILES Code [Na+].[Na+].S=C1[N-][N-]C(=S)S1, MW = 194.2 g/mol
Target chemical: 1,3,4-thiadiazole-2,5-dithiol, CAS 1072-71-5, SMILES Code S=C1N=NC(=S)S1, MW = 150.2 g/mol

3. ANALOGUE APPROACH JUSTIFICATION
It is aimed to use data on disodium 1,3,4-thiadiazole-2,5-dithiolate to sufficiently prove that the results gained on 1,3,4-thiadiazole-2,5-dithiol itself are reliable, serve as a worst case for hazard assessment, no hence not underestimate a potential hazard and no further testing is required. As indicated under point 4 Data Matrix, both substances are small molecules with a negative estimated logPow and a high water solubility, indicating a similar absorption and distribution pattern in the body. Both substances are not irritating to the skin, which was not only shown in a dermal irritation study but further also for CAS 1072-71-5 in a skin sensitization study, which was also negative. Due to the similar behaviour on the skin, it can be concluded that CAS 55906-42-8 would also have been tested negative as a skin sensitizer, and the present study on the target substance CAS 1072-71-5 suffices for hazard assessment. CAS 1072-71-5 should be classified as acute tox. oral Cat. 4, whereas the RA substance CAS 55906-42-8 does not need to be classified, clearly showing that the available study on the registered substance itself does not underestimate a possible hazard. Similar applies to eye irritation, CAS 1072-71-5 must be classified as eye dam. Cat. 1, CAS 55906-42-8 does not.

4. DATA MATRIX
The following table shows the available data relevant to justify the read-across from the source to the target chemical to demonstrate that the available studies on the registered substance itself do not underestimate a possible hazard for the endpoints acute toxicity oral, skin and eye irritation, and skin sensitization:

Endpoint Source: CAS 55906-42-8 Target: CAS 1072-71-5
Molecular weight 194.2 g/mol 150.2 g/mol
Physical state solid solid
Partition coefficient logPow = -2.3734 (EpiSuite estimation) logPow = -0.6349 (EpiSuite estimation)
Water solubility 1e+006 mg/L 2.638e+005 mg/L
Acute toxicity oral LD50 = 2955 mg/kg (rat) LD50 = 930 mg/kg (rat)
Skin irritation Not irritating (in vivo, rabbit) Not irritating (in vivo, rabbit)
Eye irritation Not irritating (in vivo, rabbit) Eye Dam. Cat. 1 (in vivo, rabbit)
Skin sensitization n/a Not sensitizing, not a skin irritant
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: 16 CFR Section 1500.42
Version / remarks:
The methods employed in the testing, evaluation and in the grading of the test material are similar to those described in Section 1500.42 - Federal Hazardous Substances Act Regulation CFR 16 P. 125.
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
other: Albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: young adult
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94--279) 9 CFR Part 3.
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
The first six rabbits did not have their eyes washed subsequent to instillation. The remaining three rabbits had the treated eyes washed after 30 seconds for 1 minute with tepid water (rate of flow approximately 1000 ml/minute).
Observation period (in vivo):
The treated eyes were examined at one, two, three, five, and seven days following instillation and washout of the test material into the eyes.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The first six rabbits did not have their eyes washed subsequent to instillation. The remaining three rabbits had the treated eyes washed after 30 seconds for 1 minute with tepid water (rate of flow approximately 1000 ml/minute).

SCORING SYSTEM: Interpretation of the results was made in accordance with the Draize Scale of Scoring Ocular Lesions.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Remarks:
Redness
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Based on the accompanying tables, the subject material is not a primary ocular irritant within the definition of the Act-Reference: Section 1500.42 (b)(1)(2) and requires no cautionary labelling with respect to that section.
The material is not an ocular irritant in the unwashed eye. Washing does not appear to make a difference.
Interpretation of results:
GHS criteria not met
Conclusions:
Study was performed scientifically reasonable similar to that described in Section 1500.42 ― Federal Hazardous Substances Act Regulations ― 16 CFR - P. 125 on a 30% aqueous solution of disodium 1,3,4-thiadiazole-2,5-dithiolate, and is sufficiently documented. Hence, the results can be considered as reliable to assess the irritating potential of disodium 1,3,4-thiadiazole-2,5-dithiolate on the rabbit eye in vivo.
In none of the animals in none of the scores, no indication of irritation was observed. Hence, it can be concluded that disodium 1,3,4-thiadiazole-2,5-dithiolate is not an eye irritant and does not need to be classified as such acc. Regulation 1272/2008.
Executive summary:

In a primary eye irritation study (16 CFR Section 1500.41), 0.1 ml of a 30% aqueous solution of disodium 1,3,4-thiadiazole-2,5-dithiolate was instilled into the conjunctival sac of the right eye of young albino rabbits. In six rabbits, the eye was not washed out, in 3 the eye was rinsed after 30 seconds. Animals then were observed for 21days.  Irritation was scored by the method of Draize.

In none of the animals in none of the scores, no indication of irritation was observed. Hence, it can be concluded that disodium 1,3,4-thiadiazole-2,5-dithiolate is not an eye irritant and does not need to be classified as such acc. Regulation 1272/2008.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

There are two reliable studies on skin irritation in the rabbit available, one on the registered substance itself, one on the read-across substance 30% disodium 1,3,4-thiadiazole-2,5-dithiolate in water. Both studies consistently reveal that the respective substance is not irritating, no indication of irritation in any of the animals at any point of time was observed. Hence, the substance 1,3,4-thiadiazole-2,5-dithiol does not need to be classified as irritating to the skin.

Further, there are two reliable studies on eye irritation in the rabbit available, one on the registered substance itself, one on the read-across substance 30%disodium 1,3,4-thiadiazole-2,5-dithiolate in water. Also the read-across substance induced not any sign of eye irritation, the undiluted registered substance 1,3,4-thiadiazole-2,5-dithiol showed corrosive effects. Hence, as a worst case, this study was taken into account when evaluating the need for classification.

According to Regulation 1272/2008, classification as Irreversible effects on the eye/serious damage to eyes (Category 1), If, when applied to the eye of an animal, a substance produces:

— at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days; and/or

— at least in 2 of 3 tested animals, a positive response of:

— corneal opacity ≥ 3 and/or

— iritis > 1,5

calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

Further, these observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test, and lesions are not fully reversible within a 21-day observation period.

An OECD 405 guideline study suffices for classification, and according to the guideline, a substance shall not be removed for 24h, solids not until 1 hour after application unless corrosion effects are noted. Hence, the results gained with animals No 7-9 cannot be used for classification, as the substance was washed out after 30 seconds. So classification must be based on the results obtained from animals No 1-6 as here the substance was not washed out. In all six animals a corneal opacity score of 4 was observed in at least one time point, all observed effects were not fully reversible after 21 days, mean corneal opacity was ≥ 3 in 5/6 animals, and iritis was also > 1,5 in 5/6 animals. Hence, the substance must be classified as Eye dam. Cat. 1.