Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2017-10-23 to 2018-01-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 17th December 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name: 1,3,5-Tris-(3-mercaptopropyl)isocyanurate
- CAS: 78366-85-5
- Purity: 94.5% (HPLC)
- Batch No: SG0117
- Molecular weight: 351.5 g/mol
- Physical state: liquid
- Colour: colourless
- Storage conditions: room temperature
Specific details on test material used for the study:
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
The required amount of the test substance was weighed by an electronic balance and placed in a tube. A small amount of vehicle 1, DMSO (20% final DMSO concentration), was added and mixed using a vortex mixer until dissolved. Vehicle 2, corn oil, was added to yield the desired concentrations (30 and 200 mg/mL). All preparations were conducted just prior to use.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Samtako Bio Korea, 105, Seorang-ro, Osan-si, Gyeonggi-do, 18100, Korea
- Females (if applicable) nulliparous and non-pregnant: Not specified
- Age at study initiation: 8–9 weeks
- Weight at study initiation: 187.73 - 219.05 g
- Fasting period before study: 16 h
- Housing: The animals were kept in groups in individually polycarbonate cage with stainless-steel cage lid, 270W x 500D x 200H (mm)
- Diet (e.g. ad libitum): Pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C), ad libitum
- Water (e.g. ad libitum): Public tap water in Asan-si was filtered and irradiated by ultraviolet light, ad libitum
- Acclimation period: six days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0 - 25.0
- Humidity (%): 31.5 - 69.8
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Vehicle 1: Dimethyl sulfoxide (DMSO) Vehicle 2: Corn oil
Details on oral exposure:
VEHICLE 1: Dimethyl sulfoxide (DMSO)
- Justification for choice of vehicle: the vehicle was chosen because it has no toxic effect on the test system under condition of this study
- Lot/batch no. (if required): Sigma Aldrich, lot no. SHBC1370V (expiry date: 13 June 2022)

VEHICLE 2: Corn oil
- Justification for choice of vehicle: the vehicle was chosen because it has no toxic effect on the test system under the condition of this study and the test substance dissolved in vehicle 1 was suspended in this vehicle 2.
- Lot/batch no. (if required): Sigma Aldrich, lot no. MKBW9504V (expiry date: 15 November 2021)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose level for this study was selected as 300 mg/kg bw because there was not any available toxicity information on the test substance.
Doses:
300, 2000 mg/kg bw
No. of animals per sex per dose:
3 females per step, 2 steps
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: All animals were observed for mortality, general condition and clinical signs (type, severity, time of onset and recovery) for 30 minutes after dosing and at 1, 2, 4 and 6 hours after dosing on the day of dosing (day 0) and once daily thereafter for 14 days (Day 1 to Day 14).
- Frequency of weighing: The animals were weighed on day 0 (prior to the administration), on days 1, 3 and 7 and on the day of the necropsy (day 14)
- Necropsy of survivors performed: On day 14, all surviving animals were anesthetized with CO2 gas and exsanguinated from the caudal vena cava and abdominal aorta. Complete gross postmortem examinations were performed on all animals in the study. Since no gross findings were observed at necropsy, histopathological examinations were not performed.
Statistics:
Statistical analysis was not performed. Mean scores and values were presented.

Results and discussion

Preliminary study:
n.a.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: at the limit dose of 2000 mg/kg bw all animals died.
Mortality:
All animals survived the duration of the study at 300 mg/kg bw. Three animals at 2000 mg/kg bw died on Day 1 after dosing.
Clinical signs:
During the observation period, dirty nose and soild perineal region were evident on Day 2, 3 and 4 after dosing at 300 mg/kg bw. Weakening and soft stool were evident in one animal 6 hours after dosing to 2000 mg/kg bw. All animals were found dead in prone position, lacrimation and soild perineal region on Day 1 after dosing at 2000 mg/kg bw. These clinical signs were considered to be test substance-related effects.
Body weight:
During the observation period, decreases in body weight were evident in three animals on Day 3 after dosing at 300 mg/kg bw. Then, these animals returned to normal on Day 7. And decreases in body weight were evident in other three animals from Day 1 to Day 3 after dosing at 300 mg/kg bw. Then, these animals returned to normal on Day 7.
Gross pathology:
At necropsy, no treatment-related macroscopic findings were observed in any animal in either step.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity study in rats conducted according to OECD 423, no mortality occurred at a dose of 300 mg/kg bw. At the limit dose of 2000 mg/kg bw all animals died. Based on the results and in accordance with OECD guideline 423 the LD50 cut-off value was determined to be 500 mg/kg bw. Thus, the substance meets the criteria of the CLP regulation 1272/2008 for being classified as Acute Tox. 4, H302.
Executive summary:

In an acute oral toxicity study (acute toxic class method, OECD 423), three groups of fasted, 8 - 9 weeks old, female Sprague-Dawley rats (3 rats/step) were given a single oral dose of the test item (94.5 % purity) in corn oil at 300 (step 1 and 2) or 2000 mg/kg bw (step 3) and were observed for 14 days. All animals treated with 300 mg/kg bw survived until the end of the study and showed only mild signs of toxicity. All three animals dosed with 2000 mg/kg bw died. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step. Based on the results and in accordance with OECD guideline 423 the LD50 cut-off value was determined to be 500 mg/kg bw. Thus, the substance meets the criteria of the CLP regulation 1272/2008 for being classified as Acute Tox. 4, H302.