1,3,4-thiadiazole-2,5-dithiol

Eye irritation

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

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

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 / tissue source

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.

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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.

Applicant's summary and conclusion

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.