Trimethylsulfonium bromide

Endpoint summary

Description of key information

The acute oral LD₅₀ in rats for Trimethylsulfonium bromide was estimated to be between 50 and 300 mg/kg b.w., and the cut-off value of LD₅₀ was estimated to be 200 mg/kg b.w..

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 06 to 23 July 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

Batch No.: 20SP9-1
Purity: 98.6%

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable)
- Source: SPF(Beijing) Biotechnology Co., Ltd.
- Females (if applicable) nulliparous and non-pregnant: yes
- Rationale for use of males (if applicable)
- Age at study initiation: 49-56 days on arrival, 57-67 days at the commencement of each animal’s dosing
- Weight at study initiation: 202~215 g at arrival, 182~246 g at the commencement of each animal’s dosing
- Fasting period before study: Food was removed overnight prior to dosing and returned approximately three to four hours after dosing.
- Housing: Animals were housed in Room D125 of the facility’s barrier system. Animals were raised in suspended, stainless steel cages (L32.0cm ×W28.0cm×H20.0cm) on cage racks (L167.0cm×W70.0cm×H171.0cm). There were 10 cages per layer, and 4 layers per rack. Animals were housed individually during the test.
- Historical data:
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days prior to the test
- Microbiological status when known
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0-25.3oC (target value 22±25oC)
- Humidity (%): 53%-73% (target value 40%-70%)
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Route of administration:

oral: gavage

Details on oral exposure:

Dosing: The prepared formulations were administrated to animals’ stomachs using standard gavage tubes attached to disposal syringes.
Dosing Frequency: Each animal was dosed once.
Dosing Volume: The dosing volume was calculated according to the fasted body weight weighed before dosing.
Dosing Time: In the morning

Doses:

The first step dosing was 300 mg/kg b.w. and 3 animals died, so 50 mg/kg b.w. was selected as the second step dosing and no animals died. Thus, 50 mg/kg b.w. was selected as the third step dosing and no animals died, the study procedure completed.

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Inspections were made twice daily, in the morning and afternoon, during normal working days (except that it was made once at necropsy days), and once daily at weekends and public holidays.
Clinical observations were performed at least once during the first 30 minutes, and at about 1, 2 and 4 hours after applications, and then once each day for 14 days.
General observations were made once daily for the animals have not been administrated with the test item.
Careful observations and records of animal fur changes, eyes and mucosa, respiratory, circulatory, autonomic and central nervous system, particularly limb activity and behavior changes were made. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhea, lethargy, sleep and coma.
Individual weights of animals were determined within 24 hours after arrival, at grouping, on Day -1, Day 0 (day of dosing), Day 7 and Day 14. At the end of the test surviving animals were weighed.
- Necropsy of survivors performed:
Animals surviving to the end of the study were anesthetized by CO2 and bled by abdominal aorta to death. Gross necropsies were performed on all animals under test. The necropsy included carefully eye examinations of the abdominal, thoracic organs and their contents of all animals.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

Dose Level-The first dosing (300 mg/kg b.w.): All animals died during the test and the mortality was 3/3.
Dose Level-The second dosing (50 mg/kg b.w.): There were no deaths or moribund status of any of the animals during the test and the mortality was 0/3.
Dose Level-The third dosing (50 mg/kg b.w.): There were no deaths or moribund status of any of the animals during the test and the mortality was 0/3.

Clinical signs:

other: All animals showed abnormal symptoms of low spontaneous movement at 1 hour after administration and died at 2 hours after administration.

Body weight:

other body weight observations

Remarks:

All survived animals showed expected gains in body weights during the test.

Gross pathology:

No abnormalities were found in all animals at necropsies.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute LD50 was estimated to be between 50 to 300 mg/kg b.w.. and Cut-off value of LD50 was estimated to be 200 mg/kg b.w.

Executive summary:

The study was performed to assess the acute oral toxicity with Trimethylsulfonium bromide in Sprague Dawley rats. The method was designed to meet the OECD Guideline for Testing of Chemicals: Acute Oral Toxicity-Acute Toxic Class Method (TG 423, adopted 2001).

Based on the results, the acute oral LD₅₀ in rats for Trimethylsulfonium bromide was estimated to be between 50 and 300mg/kg b.w., and the cut-off value of LD₅₀ was estimated to be 200 mg/kg b.w.. According to the GHS’s classification criteria for acute oral toxicity, the test item was classified as “Category 3”.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 50 - < 300 mg/kg bw

Quality of whole database:

reliable without restrictions

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A study was performed to assess the acute oral toxicity with Trimethylsulfonium bromide in Sprague Dawley rats. The method was designed to meet the OECD Guideline for Testing of Chemicals: Acute Oral Toxicity-Acute Toxic Class Method (TG 423, adopted 2001).

Based on the results, the acute oral LD₅₀ in rats for Trimethylsulfonium bromide was estimated to be between 50 and 300mg/kg b.w., and the cut-off value of LD₅₀ was estimated to be 200 mg/kg b.w.. According to the GHS’s classification criteria for acute oral toxicity, the test item was classified as “Category 3”.

No study available for dermal and inhalation route.

Justification for classification or non-classification

Acute toxicity:

Oral, OECD 423: 50 < LD50 < 300 mg/kg body weight

Therefore in accordance with Regulation (EC) No. 1272/2008 (amended by 286/2011) Table 3.1.1 , this substance should be classified as Acute toxicity Category 3.

 

Specific target organ toxicity-single exposure:

Oral:

Clinical Observations: All animals showed abnormal symptoms of low spontaneous movement at 1 hour after administration and died at 2 hours after administration.

Necropsy: No abnormalities were found in all animals at necropsies.

As there were no effects considered to support classification for Category 1 and 2 observed. Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.8.1 and 3.8.2, this substance should not be classified.