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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1980-09-24 - 1980-10-15 (experimental phase)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

No guideline stated, given information allows the conclusion the study was well performed similar to adopted guidelines.

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:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

1980-09-24 - 1980-10-15 (experimental phase)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

No guideline stated, given information allows the conclusion the study was well performed similar to adopted guidelines. 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 401 (Acute Oral Toxicity)

Deviations:

not applicable

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Sherman-Wistar albino rats

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200-300g
- Fasting period before study: The rats were deprived of food but not water overnight prior to dosing.
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CPR Part 3.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% w/v suspension in corn oil

Doses:

0.25, 0.50, 1.0, 2.0, 4.0 g/kg

No. of animals per sex per dose:

5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality daily, weight at the beginning and after 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight

Statistics:

The LD50 was calculated employing the Thompson Moving Average Method as modified by Weil, (Biometrics, September, 1952, Vol. 8, No. 3, page 249-263).

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

930 mg/kg bw

Based on:

test mat.

95% CL:

>= 660 - <= 1 310

Mortality:

Observed, 3/5 rats at 2 g/kg, 5/5 at 4 g/kg

Clinical signs:

other: 0.25 gm/kg: No untoward symptoms were observed. 0.50 gm/kg: No untoward symptoms were observed during the first 4-6 hours. After 24 hours the animals were slightly ruffled and dirty . They appeared normal within 48 hours. 1.0 gm/kg: After 4-6 hours the an

Gross pathology:

Gross pathologic examination of the 4 g/kg group revealed nothing remarkable.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Study was performed scientifically reasonable similar to OECD TG 401 on 1,3,4-Thiadiazole-2,5-dithiole, and is sufficiently documented. Hence, the results can be considered as reliable to assess the acute oral toxicity of 1,3,4-Thiadiazole-2,5-dithiole towards rats. The LD50 was determined as 0.93 (0.66 - 1.31) g/kg, which is within the boundary values of 300 and 2000 mg/kg, which triggers according to Regulation 1272/2008 the classification as acute toxic Cat. 4.

Executive summary:

In an acute oral toxicity study similar to OECD 401, groups of fasted, male Sherman-Wistar rats (5/group) were given a single oral dose of 1,3,4-Thiadiazole-2,5-dithiole, 50% in corn oil at doses of 250, 500, 1000, 2000, 4000 mg/kg bw and observed for 14 days.

The LD50 was determined as 0.93 (0.66 - 1.31) g/kg in males .

1,3,4-Thiadiazole-2,5-dithiole is of slight Toxicity based on the LD50 in males and needs to be classified as acute toxic oral Cat. 4.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

not applicable

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

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

Test animals

Species:

rat

Strain:

other: Sherman-Wistar albino rats

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200-300g
- Fasting period before study: The rats were deprived of food but not water overnight prior to dosing.
- Housing: The animals were housed and maintained in compliance with the Animal Welfare Act (Pub. L-94-279) 9 CPR Part 3.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% w/v suspension in corn oil

Doses:

0.25, 0.50, 1.0, 2.0, 4.0 g/kg

No. of animals per sex per dose:

5 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality daily, weight at the beginning and after 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: body weight

Statistics:

The LD50 was calculated employing the Thompson Moving Average Method as modified by Weil, (Biometrics, September, 1952, Vol. 8, No. 3, page 249-263).

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

930 mg/kg bw

Based on:

test mat.

95% CL:

>= 660 - <= 1 310

Mortality:

Observed, 3/5 rats at 2 g/kg, 5/5 at 4 g/kg

Clinical signs:

other: 0.25 gm/kg: No untoward symptoms were observed. 0.50 gm/kg: No untoward symptoms were observed during the first 4-6 hours. After 24 hours the animals were slightly ruffled and dirty . They appeared normal within 48 hours. 1.0 gm/kg: After 4-6 hours the an

Gross pathology:

Gross pathologic examination of the 4 g/kg group revealed nothing remarkable.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Study was performed scientifically reasonable similar to OECD TG 401 on 1,3,4-Thiadiazole-2,5-dithiole, and is sufficiently documented. Hence, the results can be considered as reliable to assess the acute oral toxicity of 1,3,4-Thiadiazole-2,5-dithiole towards rats. The LD50 was determined as 0.93 (0.66 - 1.31) g/kg, which is within the boundary values of 300 and 2000 mg/kg, which triggers according to Regulation 1272/2008 the classification as acute toxic Cat. 4.

Executive summary:

In an acute oral toxicity study similar to OECD 401, groups of fasted, male Sherman-Wistar rats (5/group) were given a single oral dose of 1,3,4-Thiadiazole-2,5-dithiole, 50% in corn oil at doses of 250, 500, 1000, 2000, 4000 mg/kg bw and observed for 14 days.

The LD50 was determined as 0.93 (0.66 - 1.31) g/kg in males .

1,3,4-Thiadiazole-2,5-dithiole is of slight Toxicity based on the LD50 in males and needs to be classified as acute toxic oral Cat. 4.