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Toxicological information

Acute Toxicity: oral

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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.

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:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Sherman-Wistar albino rats
Sex:
male
Details on test animals 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:
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 animals appeared slightly ruffled. They were lethargic and dirty after 24 hours. Within 48 hours they appeared essentially normal.
2.0 gm/kg: After 2-4 hours the animals were slightly depressed and ruffled. Their general condition had worsened after 24 hours with greater depression and ataxia being evident. Within 48 hours some of the animals appeared moribund. Deaths occurred as noted on the third day and the remaining animals were in poor health. An additional death occurred on the fifth day. The two surviving animals appeared essentially recovered after 7-8 days.
4.0 gm/kg: After 2 hours the animals were severely depressed. Several animals became semi-comatose after 6 hours. Deaths occurred over several days as noted.
Body weight:
no effects stated
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.