4-amino-N-[4-(aminocarbonyl)phenyl]benzamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well performed GLP and OECD guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-amino-N-[4-(aminocarbonyl)phenyl]benzamide

EC Number:

277-874-7

EC Name:

4-amino-N-[4-(aminocarbonyl)phenyl]benzamide

Cas Number:

74441-06-8

Molecular formula:

C14H13N3O2

IUPAC Name:

4-amino-N-(4-carbamoylphenyl)benzamide

Details on test material:

- Name of test material (as cited in study report): p-Aminobenzoylaminobenzamid TF

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Test Animals:
Animals: Rat, RccHan: WIST(SPF)
Rationale: Recognized by international guidelines as a recommended test system.
Breeder: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands, Postbus 6174, 5960 AD Horst / The Netherlands
Age (when treated): 10 weeks
Body Weight Range (when treated): 176.3 g – 199.7 g
Randomization: Selected by hand at time of delivery. No computer generated randomization program.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.


Environmental Conditions:
room temperature: 22 ± 3 °C
relative humidity: 30-70%,
light cycle: 12 hours light and 12 hours dark, music during the daytime light period.
Accommodation: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding
Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 15/09 ad libitum
Water: Community tap water from Füllinsdorf ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The animals received a single dose of the test item by oral gavage administration at 2000 mg/kg body weight after being fasted for approximately 17 to 19 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing.
The dosing volume was 10 mL/kg body weight.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

2 dose groups, 3 females per dose group

Control animals:

no

Details on study design:

Preparation of Dose Formulations:
Dose levels are in terms of the test item as supplied by the Sponsor. The dose formulations were prepared shortly before each dosing occasion using a magnetic stirrer and a spatula as homogenizers. The test item was weighed into a tared glass beaker on a suitable precision balance and the
vehicle added (weight:volume). Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Vehicle:
Purified water was found to be a suitable vehicle. The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. This formulation trial is excluded from the statement of compliance.

Observations:
Viability / Mortality: Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (in common with the clinical signs) and twice daily during days 2-15.
Clinical Signs: Daily during the acclimatization period, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1, depending on the occurrence of clinical signs of toxicity. Once daily during days 2-15.
Body Weights: On test days 1 (prior to administration), 8 and 15.

Necropsy:
All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

other: All animals showed slightly ruffled fur and hunched posture immediately after treatment. Hunched posture persisted one to several hours following the treatment and ruffled fur was noted in all animals until week two. No clinical signs were observed in any

Gross pathology:

No macroscopic findings were recorded at necropsy.

Any other information on results incl. tables

LD50 cut-off (mg/kg b.w.): ∞, unclassified

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: expert judgment

Conclusions:

The median lethal dose of p-Aminobenzoylaminobenzamid TF after single oral administration to female rats, observed over a period of 14 days, is:

LD50 (female rat): greater than 2000 mg/kg body weight

LD50 cut-off (mg/kg b.w.): ∞, unclassified

Executive summary:

Two groups, each of three female RccHan: WIST (SPF) rats, were treated with p-Aminobenzoylaminobenzamid TF by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in purified water at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 and once daily during test days 2-15. Mortality/viability was recorded within the first 30 minutes and approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during test days 2-15. Body weights were recorded on test day 1 (prior to administration) and on test days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the observation period.

All animals showed slightly ruffled fur and hunched posture immediately after treatment. Hunched posture persisted one to several hours following the treatment and ruffled fur was noted in all animals until week two. No clinical signs were observed in any animal from test day 11 onward until the end of the observation period.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were recorded at necropsy.

The median lethal dose of p-Aminobenzoylaminobenzamid TF after single oral administration to female rats, observed over a period of 14 days, is:

LD50 (female rat): greater than 2000 mg/kg body weight

LD50 cut-off (mg/kg b.w.): ∞, unclassified