Disodium 1,3,4-thiadiazole-2,5-dithiolate

Endpoint summary

Description of key information

In vivo skin irritation (read-across from CAS 1072-71-5): CFR section 1500.41, albino rabbit, occlusive, 24h, no wash-off, no signs of irritation

In vivo skin irritation: CFR section 1500.41, albino rabbit, occlusive, 24h, no wash-off, no signs of irritation

In vivo eye irritation (read-across from CAS 1072-71-5): 16 CFR section 1500.42, albino rabbit, with&without wash-out, Category 1, irreversible effects on the eye

In vivo eye irritation: 16 CFR section 1500.42, albino rabbit, with&without wash-out, no indication od irritation

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

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:

1980-09-19 - 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.

Qualifier:

according to guideline

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 or test system 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

Reference 2

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:

1980-09-30 - 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. Performed on read-across substance.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
General remarks ahead:
The substance is unstable when isolation from water and amine stabilizers and / or manufacture without water is attempted. The solid DMTD-Na is, based on handling observations, only stable as aqueous solution in combination with stabilizers as set out in IUCLID section 1.2. As a pure substance, it is highly unstable towards oxygen (after contact the corresponding dimer is formed), and very hygroscopic. In consequence, the substance needs to be registered including water (required for stabilization) and water is hence part of the substance ID. The substance should still be regarded as a mono-constituent substance according to the “Guidance for identification & naming of substances under REACH & CLP” (v1.3). Analytics revealed that the substance is composed of Disodium 1,3,4-thiadiazole-2,5-dithiolate (CAS 55906-42-8), water and stabilizing amines, no other DMTD-species was found. This is comparable to the structurally related read-across substance DMTD (1,3,4-Thiadiazole-2,5-dithiol, CAS 1072-71-5). Water is toxicologically irrelevant, and so, only the similarities between the two solid substances need to be regarded.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across is justified out of the following reasons:
1. The substances are structural analogues. The registered substance is produced from a neutralization reaction of 1,3,4-Thiadiazole-2,5-dithiol (CAS 1072-71-5, EC 214-014-1; source) and Sodium hydroxide (CAS 1310-73-2, EC 215-185-5) in the presence of stabilizers. So the organic ring remains intact. During analysis of DMTD-Na via HPLC, it cannot even be detected anymore but is transformed in the source substance. So the prerequisites of common functional group(s) and common precursor(s) are fulfilled.
2. The source and target substance exhibit both similar properties, or the source substance properties can be regarded as worst case, while the target substance bear toxicologically less relevant properties, see point 4. Data Matrix.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
For the properties of the target substance, please refer to section 1.2
Property Source chemical Target Chemical
CAS RN 1072-71-5 55906-42-8
Name 1,3,4-Thiadiazole-2,5-dithiol Disodium 1,3,4-thiadiazole-2,5-dithiolate
EC-No. 214-014-1 259-886-4
Other contained substances None; substance is pure Water
Stabilizing amines (see section 1.2), either not classified or not contained to a relevant amount
In both substances, only the substance was found analytically. There was no indication that possibly dimers or other oligomeric substances are present.

3. ANALOGUE APPROACH JUSTIFICATION
First, the substances are structural analogues. They have common functional group(s) and common precursor(s). Second, the impurity profile does not hinder the read-across. The source chemical is pure, and the target substance does only contain other substances which are not relevant for classification. They have the same basic structure, no dimers or oligomers are found. Third, during analysis in a slightly acidic, aqueous eluent, which is relevant for body fluids, too, the registered substance was even transformed back into the source chemical. Fourth, they have the same toxicological properties, based on the actually available information, see 4. Data matrix.

4. DATA MATRIX
Endpoint Source chemical Target Chemical
CAS RN 1072-71-5 55906-42-8
Name 1,3,4-Thiadiazole-2,5-dithiol Disodium 1,3,4-thiadiazole-2,5-dithiolate
Acute oral toxicity LD50 = 930 mg/kg (males) 9850 mg/kg (males; solution)
2955 mg/kg (males, active ingredient)
Skin irritation Not irritating Not irritating
Eye irritation Eye Dam. Cat. 1 Not irritating
It can be reasonably assumed, that the effects are similar also in ecotoxicity tests.

In summary, the read-across from 1,3,4-Thiadiazole-2,5-dithiol to Disodium 1,3,4-thiadiazole-2,5-dithiolate is justified.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

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 or test system 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 conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

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 - 1980-10-06 (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.

Qualifier:

according to guideline

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.

Reference 2

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 - 1980-10-20 (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. Performed on read-across substance.

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
General remarks ahead:
The substance is unstable when isolation from water and amine stabilizers and / or manufacture without water is attempted. The solid DMTD-Na is, based on handling observations, only stable as aqueous solution in combination with stabilizers as set out in IUCLID section 1.2. As a pure substance, it is highly unstable towards oxygen (after contact the corresponding dimer is formed), and very hygroscopic. In consequence, the substance needs to be registered including water (required for stabilization) and water is hence part of the substance ID. The substance should still be regarded as a mono-constituent substance according to the “Guidance for identification & naming of substances under REACH & CLP” (v1.3). Analytics revealed that the substance is composed of Disodium 1,3,4-thiadiazole-2,5-dithiolate (CAS 55906-42-8), water and stabilizing amines, no other DMTD-species was found. This is comparable to the structurally related read-across substance DMTD (1,3,4-Thiadiazole-2,5-dithiol, CAS 1072-71-5). Water is toxicologically irrelevant, and so, only the similarities between the two solid substances need to be regarded.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across is justified out of the following reasons:
1. The substances are structural analogues. The registered substance is produced from a neutralization reaction of 1,3,4-Thiadiazole-2,5-dithiol (CAS 1072-71-5, EC 214-014-1; source) and Sodium hydroxide (CAS 1310-73-2, EC 215-185-5) in the presence of stabilizers. So the organic ring remains intact. During analysis of DMTD-Na via HPLC, it cannot even be detected anymore but is transformed in the source substance. So the prerequisites of common functional group(s) and common precursor(s) are fulfilled.
2. The source and target substance exhibit both similar properties, or the source substance properties can be regarded as worst case, while the target substance bear toxicologically less relevant properties, see point 4. Data Matrix.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
For the properties of the target substance, please refer to section 1.2
Property Source chemical Target Chemical
CAS RN 1072-71-5 55906-42-8
Name 1,3,4-Thiadiazole-2,5-dithiol Disodium 1,3,4-thiadiazole-2,5-dithiolate
EC-No. 214-014-1 259-886-4
Other contained substances None; substance is pure Water
Stabilizing amines (see section 1.2), either not classified or not contained to a relevant amount
In both substances, only the substance was found analytically. There was no indication that possibly dimers or other oligomeric substances are present.

3. ANALOGUE APPROACH JUSTIFICATION
First, the substances are structural analogues. They have common functional group(s) and common precursor(s). Second, the impurity profile does not hinder the read-across. The source chemical is pure, and the target substance does only contain other substances which are not relevant for classification. They have the same basic structure, no dimers or oligomers are found. Third, during analysis in a slightly acidic, aqueous eluent, which is relevant for body fluids, too, the registered substance was even transformed back into the source chemical. Fourth, they have the same toxicological properties, based on the actually available information, see 4. Data matrix.

4. DATA MATRIX
Endpoint Source chemical Target Chemical
CAS RN 1072-71-5 55906-42-8
Name 1,3,4-Thiadiazole-2,5-dithiol Disodium 1,3,4-thiadiazole-2,5-dithiolate
Acute oral toxicity LD50 = 930 mg/kg (males) 9850 mg/kg (males; solution)
2955 mg/kg (males, active ingredient)
Skin irritation Not irritating Not irritating
Eye irritation Eye Dam. Cat. 1 Not irritating
It can be reasonably assumed, that the effects are similar also in ecotoxicity tests.

In summary, the read-across from 1,3,4-Thiadiazole-2,5-dithiol to Disodium 1,3,4-thiadiazole-2,5-dithiolate is justified.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

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 conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

Both available studies on the registered substance itself did not show any signs of irritation / corrosion. Hence, the substance does not need to be classified as skin or eye irritant according to Regulation 1272/2008 and amendments.