1,3,5-triazine-2,4,6(1H,3H,5H)-trithione

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,3,5-triazine-2,4,6(1H,3H,5H)-trithione

EC Number:

211-322-8

EC Name:

1,3,5-triazine-2,4,6(1H,3H,5H)-trithione

Cas Number:

638-16-4

Molecular formula:

C3H3N3S3

IUPAC Name:

1,3,5-triazine-2,4,6(1H,3H,5H)-trithione

Test animals

Species:

rat

Strain:

other: Sprague-Dawley (Crl; CD (SD), SPF

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 weeks at study initiation / 8 weeks at test item administration
- Weight at study initiation: 9 females 258.4 - 183.6 g
- Fasting period before study: 16 hours
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.0 - 24.5° C
- Humidity (%): 49 - 59%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 24.05.2005 To: 14.06.2005

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% carboxymethyl cellulose sodium solution

Doses:

300 mg/kg and 2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days (administration day was taken as observation day 1)
- Frequency of observations: First and second stage (300 mg/kg) 30 min, 60 min, 2 h, 3 h, 4 h, 5 h, 6 h and once daily thereafter; third stage (2000 mg/kg) 30 min, 60 min, 90 min, 120 min, 150 min, 180 min, 4 h, 5 h, 6 h and once daily thereafter
- Frequency of weighing: First and second stage (300 mg/kg): day 1 (dosage administration day), day 2, day 4, day 8, day 11 and day 15
Third stage (2000 mg/kg): day 1 (before administration), day 2, day 3, day 4
- Necropsy of survivors performed: yes
- Other examinations performed: gross examination of organs at necropsy, organ weights, histopathology

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: according to OECD 423

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 150 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg bw (stage 1): 0/3
300 mg/kg bw (stage 2): 0/3
2000 mg/kg bw (stage 3): 3/3

At 2000 mg/kg bw mortalities occurred in 1 case after about 2 hours after dosage, the 2 remaining test animals died on the third and fourth observation day.
No mortality occurred following a single oral administration of 300 mg/kg bw trithiocyanuric acid.

Clinical signs:

other: No toxicity was displayed in rat with a single oral administration of 300 mg/kg trithiocyanuric acid, but with 2000 mg/kg bw administration clearly lead to the death of the animal system.

Gross pathology:

Full body rigor was identified immediately after death in the one animal that died within about 2 hours after administering 2000 mg/kg bw. Contamination of perirhinal hair, enlargement of kidney, spleen and adrenal gland, and downsizing of pancreas were identified in the 2 animals that died on the 3rd and 4th observation day, and a dark red region in the lung was identified in the animal that died on the 3rd observation day. The stomach revealed whitish liquid residues in the animals, that died on the administration day and on the 3rd observation day after administration of 2000 mg/kg bw. Furthermore, the right atrium was filled with blood in all 3 rats, that died.
No abnormal findings were noted in animals dosed with 300 mg/kg bw.

Other findings:

Histopathology:
Histopathology was restricted to animals administered 2000 mg/kg bw.
Proximal tubular epithelium cortical substance degeneration/necrosis as well as cortical glumerular degeneration/necrosis and edema in the papilla region was identified in all three animals. In the rats, which died on the 3rd and 4th observation day, medullary collecting duct epithelium degeneration/necrosis, necrosis of the papilla and cell infiltration in blood vessels was observed and was also seen in the hyaline droplets in the glomerular of the papillary region. In addition, mineral deposits in the cortical layer and hyaline cylinder in the medulla were identified in these two animals. In the animal that died on the 3rd observation day the cortical distale tubule lumen was extended.
Very slight to slight extramedullary haemopoeisis and lipofuscin sediment in all animals were noted in the pancreas. A clear reduction of the spleen white pulp region was identified in the rats, that died on the 3rd and 4th observation day.
Congestion was observed in all animals' lung.
In the lung, edema and aggregation of foamy cells in alveoli were noted in the animals, that died on the 3rd and 4th observation day. In addition, the animal that died on the 3rd observation day infiltration of neutrophilic leukocytes in the alveolar septa was found.
Periportal fat in liver cells and vascular degeneration of liver cells in lobules were seen in all three animals.
No histopathological findings were observed in heart, brain and stomach.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In this acute oral toxicity study in the female rat a cut-off LD50 value of 500 mg/kg bw was found. In addition the LD50 was calculated to be 1150 mg/kg bw.