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EC number: 259-886-4 | CAS number: 55906-42-8
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Remarks:
- In vivo study performed prior (1980) to REACH implementation and adoption of LLNA test guideline.
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1980-10-06 - 1980-11-12 (experimental phase)
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Justification for type of information:
- REPORTING FORMAT FOR THE ANALOGUE APPROACH
see target record
Cross-reference
- Reason / purpose for cross-reference:
- read-across source
- Remarks:
- link to target
Reference
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Remarks:
- In vivo study performed prior (1980) to REACH implementation and adoption of LLNA test guideline.
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- 1980-10-06 - 1980-11-12 (experimental phase)
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- 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:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- not applicable
- GLP compliance:
- not specified
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- In vivo guinea pig study was performed prior (1980) to REACH implementation and adoption of LLNA test guideline.
- Species:
- guinea pig
- Strain:
- other: Albino
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 300 - 400 g
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR Part 3.
- Indication of any skin lesions: none stated - Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0.5 g
- Day(s)/duration:
- 10 application, every second day
- Adequacy of induction:
- other: highest possible concentration (undiluted material), non-irritant
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0.5 g
- Day(s)/duration:
- 24 h
- Adequacy of challenge:
- other: highest possible concentration (undiluted)
- No. of animals per dose:
- 5 males & 5 females
- Details on study design:
- MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 24h exposure
- Test groups: group of ten (five male and five female rats)
- Control group: none stated
- Site: intact skin test sites
- Frequency of applications: every second day
- Duration: 19 days
- Concentrations: undiluted
B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: At the termination of the 2 week rest period a challenge application was put on skin sites differing from the original test sites. The challenge application remained on for 24 hours.
- Exposure period: 24h
- Test groups: group of ten (five male and five female rats)
- Site: skin sites differing from the original test sites
- Concentrations: undiluted
- Evaluation (hr after challenge): 24h & 48h - Challenge controls:
- none stated
- Positive control substance(s):
- not required
- Positive control results:
- n/a
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- undiluted
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no effects stated
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- undiluted
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no effects stated
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 1st & 2nd reading
- Group:
- negative control
- Remarks on result:
- other: information not given
- Reading:
- other: 1st & 2nd reading
- Group:
- positive control
- Remarks on result:
- other: information not given
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Study was performed scientifically reasonable similar OECD TG 406 on 1,3,4-Thiadiazole-2,5-dithiole, is sufficiently documented, and taking into account the obtained results with acceptable restrictions. Hence, the results can be considered as reliable to assess the sensitizing potential of 1,3,4-Thiadiazole-2,5-dithiole in guinea pigs.
The undiluted test material was tested on 5 male and 5 female guinea pigs. According to OECD TG 406 regarding the Bühler test, “a minimum of 20 animals is used in the treatment group“. As the test item did not produce any sign of irritation, neither during induction nor challenge, in all the tested animals, the result can be nevertheless considered as unambiguous. Hence, the test item does not need to be classified as a skin sensitizer. - Executive summary:
In a dermal sensitization study (performed scientifically reasonable similar OECD TG 406) with unchanged 1,3,4-Thiadiazole-2,5-dithiole in 300-400 g albino guinea pigs (5/sex) were tested using the method of Bühler, irritation scoring according to Draize.
A 0.5 gm portion of material was applied to the intact skin test sites on the guinea pigs. After a 24 hour contact period (occlusive) the patch was removed and the animals were allowed to rest for one day. Exposure was repeated 10 times. After the tenth application the animals were rested for a two week period. At the termination of the rest period a challenge application was put on skin sites differing from the original test sites. The challenge application remained on for 24 hours. Twenty-four hours after each induction stage application and twenty-four and forty-eight hours after the challenge (re-test) application, the sites were examined for irritation, if any.
In none of the animals any sign of systemic toxicity, irritation or sensitization was noted after any application.
In this study, 1,3,4-Thiadiazole-2,5-dithiole is not a dermal sensitizer, no classification is required.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 980
- Report date:
- 1980
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Deviations:
- not applicable
- GLP compliance:
- not specified
- Type of study:
- Buehler test
- Justification for non-LLNA method:
- In vivo guinea pig study was performed prior (1980) to REACH implementation and adoption of LLNA test guideline.
Test material
- Reference substance name:
- 1,3,4-thiadiazole-2,5-dithiol
- EC Number:
- 214-014-1
- EC Name:
- 1,3,4-thiadiazole-2,5-dithiol
- Cas Number:
- 1072-71-5
- Molecular formula:
- C2H2N2S3
- IUPAC Name:
- 1,3,4-thiadiazole-2,5-dithiol
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- other: Albino
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 300 - 400 g
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CFR Part 3.
- Indication of any skin lesions: none stated
Study design: in vivo (non-LLNA)
Induction
- Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0.5 g
- Day(s)/duration:
- 10 application, every second day
- Adequacy of induction:
- other: highest possible concentration (undiluted material), non-irritant
Challenge
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- unchanged (no vehicle)
- Concentration / amount:
- 0.5 g
- Day(s)/duration:
- 24 h
- Adequacy of challenge:
- other: highest possible concentration (undiluted)
- No. of animals per dose:
- 5 males & 5 females
- Details on study design:
- MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10
- Exposure period: 24h exposure
- Test groups: group of ten (five male and five female rats)
- Control group: none stated
- Site: intact skin test sites
- Frequency of applications: every second day
- Duration: 19 days
- Concentrations: undiluted
B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: At the termination of the 2 week rest period a challenge application was put on skin sites differing from the original test sites. The challenge application remained on for 24 hours.
- Exposure period: 24h
- Test groups: group of ten (five male and five female rats)
- Site: skin sites differing from the original test sites
- Concentrations: undiluted
- Evaluation (hr after challenge): 24h & 48h - Challenge controls:
- none stated
- Positive control substance(s):
- not required
Results and discussion
- Positive control results:
- n/a
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- undiluted
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no effects stated
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- undiluted
- No. with + reactions:
- 0
- Total no. in group:
- 10
- Clinical observations:
- no effects stated
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- other: 1st & 2nd reading
- Group:
- negative control
- Remarks on result:
- other: information not given
- Reading:
- other: 1st & 2nd reading
- Group:
- positive control
- Remarks on result:
- other: information not given
Applicant's summary and conclusion
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- Study was performed scientifically reasonable similar OECD TG 406 on 1,3,4-Thiadiazole-2,5-dithiole, is sufficiently documented, and taking into account the obtained results with acceptable restrictions. Hence, the results can be considered as reliable to assess the sensitizing potential of 1,3,4-Thiadiazole-2,5-dithiole in guinea pigs.
The undiluted test material was tested on 5 male and 5 female guinea pigs. According to OECD TG 406 regarding the Bühler test, “a minimum of 20 animals is used in the treatment group“. As the test item did not produce any sign of irritation, neither during induction nor challenge, in all the tested animals, the result can be nevertheless considered as unambiguous. Hence, the test item does not need to be classified as a skin sensitizer. - Executive summary:
In a dermal sensitization study (performed scientifically reasonable similar OECD TG 406) with unchanged 1,3,4-Thiadiazole-2,5-dithiole in 300-400 g albino guinea pigs (5/sex) were tested using the method of Bühler, irritation scoring according to Draize.
A 0.5 gm portion of material was applied to the intact skin test sites on the guinea pigs. After a 24 hour contact period (occlusive) the patch was removed and the animals were allowed to rest for one day. Exposure was repeated 10 times. After the tenth application the animals were rested for a two week period. At the termination of the rest period a challenge application was put on skin sites differing from the original test sites. The challenge application remained on for 24 hours. Twenty-four hours after each induction stage application and twenty-four and forty-eight hours after the challenge (re-test) application, the sites were examined for irritation, if any.
In none of the animals any sign of systemic toxicity, irritation or sensitization was noted after any application.
In this study, 1,3,4-Thiadiazole-2,5-dithiole is not a dermal sensitizer, no classification is required.
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