(1R)-2-[5-(2-halo-3-methoxyphenyl)-3-[2-halo-6-(trihalomethyl)benzyl]- 4-alkyl-2,6-dioxoheterocyclyl]-1-phenylethanaminium salicylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15th June 2018 to 7th January 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Acute Oral Toxicity - Acute Toxic Class Method (423) published by the Ministry of Environmental Protection of Peoples Republic of China in the year 2013

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

A physical check up was carried out on all animals on arrival. Healthy young animals were acclimatised to the laboratory conditions and paired housed per cage in the facility of Room D101 for 7 days prior to the test. All animals were weighed and marked on the hair. Clinical observations were performed daily until grouping. Animals were raised in suspended stainless steel cages. Animals were housed individually during the test.
Temperature: 20-25oC
Humidity: 40-70%
Light sequence: 12 hour light / 12 hour dark
Food: Sterilised diet with SPF Rodent Maintenance (Beijing keaoxieli Feed Co. Ltd.)
Water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Corn oil

Doses:

Dose volume
A-1298847: 10 mL/kg
Dose levels:
2000 mg/kg (female)

No. of animals per sex per dose:

3

Details on study design:

The test item was tested using a stepwise procedure, each group using 3 female animals. The first step of dosing was 2000 mg/kg. As there were no deaths, the second step used a dose rate of 2000 mg/kg and one animal died. Clinical observations and body weights were monitored during the study. All animals were subject to gross necroscopy.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Mortality:

One death occured in the second step

Clinical signs:

other: There were no abnormal findings during the test

Gross pathology:

There were no findings during gross necropsy in any of the main study animals at the end of study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, the test item was determined to have an estimated LD50 of 2500 mg/kg and therefore classified as a Hazard Category of 5 according to Globally Harmonized System (GHS), however, since category 5 is not recognized by the EU, the results is considered GHS criteria not met.

Executive summary:

Objective
The study was performed to assess the acute oral toxicity of A1298847.0 in  the Sprague Dawley rat.  The method was designed to meet the guidelines for the Testing of Chemicals - Acute Toxic Class Method (423) published by the Ministry of Environmental Protection of Peoples Republic of China in the year 2013. 

General Procedure
The test item was tested using a stepwise procedure, each group using 3 female animals. The first and second step dosing were both 2000 mg/kg. There was one deaths in the second testing group. Clinical observations and body weights were monitored during the study. All animals were subject to gross necroscopy.

There were no deaths in the first study (mortality 0/3).

There was one death in the second study (mortality 1/3).

There were no abnormal findings during the study. During the first step dosing, animals individual body weight decreased slightly. After the first and second week after dosing, average body weight increased. There were no findings during gross necropsy. 

Conclusions: Based on the results, the test item was determined to have an estimated LD50 of 2500 mg/kg and therefore classified as a Hazard Category of 5 according to Globally Harmonized System (GHS).