[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 Augustus 2020 - 08 October 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF), November 2000, including the most recent revisions.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N1,N3‐bis(3‐methylphenyl)‐5‐[(3‐methylphenyl)sulfamoyl]benzene‐1,3‐dicarboxamide

Molecular formula:

C29H27N3O4S

IUPAC Name:

N1,N3‐bis(3‐methylphenyl)‐5‐[(3‐methylphenyl)sulfamoyl]benzene‐1,3‐dicarboxamide

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: Off-white powder
- Storage condition: At room temperature protected from light

Test animals

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals, approximately 9 to 10 weeks old
- Weight at study initiation: 166 to 191 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item. Water was available.
- Housing: Animals were group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages containing sterilized wooden fibers as bedding material.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to municipal tap-water
- Acclimation period: at least 5 days
- Method of randomisation in assigning animals to test and control groups: Animals were assigned to the study at the discretion of the coordinating biotechnician, with all animals within ± 20% of the sex mean body weights.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70
- Air changes (per hr): 10 or greater
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 Augustus 2020 To: 30 September 2020

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Water (Elix)
- Supplier: Millipore S.A.S., Molsheim, France
- Justification for choice of vehicle: Trial preparations were performed to select the suitable vehicle and to establish a suitable formulation procedure.

MAXIMUM DOSE VOLUME APPLIED: The dose volume for each animal was based on the body weight measurement prior to dosing. A dose volume of 10 mL/kg body weight was used for each dose.

DOSAGE PREPARATION: Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements.
The dosing formulations were kept at room temperature until dosing. The dosing formulations
were stirred until and during dosing.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The first group was treated at a dose level of 300 mg/kg. Based on the results, two additional groups were dosed at 2000 mg/kg.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical Observations:
Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals for the first hour after dosing.
Mortality/Moribundity Checks:
Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.
Body Weights:
Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: All animals were sacrificed by oxygen/carbon dioxide rocedure at the end of the observation period. All animals assigned to the study were subjected to ecropsy and descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

Not performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: At 300 mg/kg, hunched posture was noted in all animals on Days 1 and 2. At 2000 mg/kg, hunched posture or erected fur was seen between Days 1 and/or 4.

Gross pathology:

Glandular, irregular surface of the stomach was found in one animal at 2000 mg/kg at macroscopic post mortem examination. No other abnormalities were found at macroscopic examination in any of the other animals.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified. According to Regulation (EC) No. 1272/2008 and its amendments.

Conclusions:

In an acute oral toxicity study with female rats, performed according to OECD 423 test guideline and
GLP principles, a LD50 >2000 mg/kg bw was determined.

Executive summary:

The substance was administered by oral gavage to three consecutive groups of three female Wistar Han rats at 300 and 2000 mg/kg body weight, performed according to OECD 423 test guideline and GLP principles.

No mortality occurred. At 300 mg/kg, hunched posture was noted in all animals on Days 1 and 2. At 2000 mg/kg, hunched posture or erected fur was seen between Days 1 and/or 4. Glandular, irregular surface of the stomach was found in one animal at 2000 mg/kg at macroscopic post mortem examination. No other abnormalities were found at macroscopic examination in any of the other animals.

Based on the results, a LD50 >2000 mg/kg bw was determined and the substance does not have to be classified for acute oral toxicity according to Regulation (EC) No. 1272/2008 and its amendments.