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Toxicological information

Eye irritation

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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:
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

Reference
Name:
Unnamed
Type:
Constituent

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

Resultsopen allclose all
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.

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.