N,N'-(2-(4-(2-aminobenzamido)butyl)pentane-1,5-diyl)bis(2-aminobenzamide)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental Phase: 16 July 2020 to 11 August 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 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Test material

Test material information

Constituent 1

Reference substance name:

2-amino-N-{6-[(2-aminophenyl)formamido]-2-{3-[(2-aminophenyl)formamido]propyl}hexyl}benzamide

EC Number:

951-985-7

Molecular formula:

C30H38N6O3

IUPAC Name:

2-amino-N-{6-[(2-aminophenyl)formamido]-2-{3-[(2-aminophenyl)formamido]propyl}hexyl}benzamide

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

other: RccHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS (UK) Ltd
- Females nulliparous and non-pregnant: yes
- Age at study initiation: eight to twelve weeks
- Weight at study initiation: 168 to 176 grams
- Fasting period before study: overnight prior to and approximately four hours after dosing
- Housing: cages were solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved softwood bark-free fiber bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.
- Diet (e.g. ad libitum): freely available standard rodent diet (Teklad 2014C Diet)
- Water (e.g. ad libitum): Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: at least five days
Method of randomisation in assigning animals to test and control groups: The animals were allocated without conscious bias to cages within the treatment groups. They were housed in groups of one or four rats.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24 °C
- Humidity (%): 40 to 70%
- Air changes (per hr): not stated butthe animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours continuous dark per 24 hours

IN-LIFE DATES: From: 16 July 2020 To: 11 August 2020.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% w/v aqueous methyl cellulose

Details on oral exposure:

VEHICLE (1% w/v aqueous methyl cellulose)
- Concentration in vehicle: 30 mg/L (300 mg/kg/ bw dose level) or 200 mg/L (2000 mg/kg/bw dose level)
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle:

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

Sighting investigations: 300 and 2000 mg/kg body weight
Main study: 2000 mg/kg body weight

No. of animals per sex per dose:

Sighting investigations: 1 animal at 300 mg/kg body weight, 1 animal at 2000 mg/kg body weight
Main study: 4 aninals at 2000 mg/kg body weight

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of any clinical signs and the time were recorded at each observation. All animals were observed for 14 days after dosing. The weight of each rat was recorded on Days -1 (not reported), 1 (prior to dosing), 8 and 15. Individual weekly body weight changes and group mean body weights were calculated.
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, macropathology

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no clinical signs of reaction to treatment throughout the study.

Gross pathology:

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal oral dose (LD50) to female rats of the test substance was demonstrated to be greater than 2000 mg/kg body weight.

Executive summary:

Introduction

The acute oral toxicity of the test substance was determined using a test method designed to meet the requirements of the following guidelines:

 

• EEC Methods for the determination of toxicity and other health effects. Commission Regulation No. 440/2008, Part B, Method B.1 bis. Acute Oral Toxicity: Fixed Dose Procedure. 30 May 2008.
  
  


• OECD Guideline for Testing of Chemicals No.420 ‘Acute Oral Toxicity – Fixed Dose Method’ Adopted 17 December 2001.


• EPA Health Effects Test Guidelines OPPTS 870.1100 Acute Oral Toxicity EPA 712‑C-02-190. December 2002.


• Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.

 

 

Method

Fasted female rats received a single oral gavage dose of the test item, formulated in 1% w/v aqueous methyl cellulose, at the following dose levels:

 

Sighting investigations: 300 and 2000 mg/kg body weight

 

Main study: Based on the results of the sighting investigations a further four fasted females were similarly dosed at 2000 mg/kg body weight.

 

During the study, clinical condition, body weight and macropathology investigations were undertaken.

 

Results

There were no deaths during the study.

 

There were no clinical signs of reaction to treatment throughout the study. All animals were considered to have achieved satisfactory body weight gains throughout the study.

 

No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

 

Conclusion

The acute median lethal oral dose (LD50) to female rats of the test substance was demonstrated to be greater than 2000 mg/kg body weight.