N,N'-1,4-phenylenebis[3-oxobutyramide]

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 study according to recent OECD TG.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (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:

N,N'-1,4-phenylenebis[3-oxobutyramide]

EC Number:

246-438-8

EC Name:

N,N'-1,4-phenylenebis[3-oxobutyramide]

Cas Number:

24731-73-5

Molecular formula:

C14H16N2O4

IUPAC Name:

3-oxo-N-[4-(3-oxobutanamido)phenyl]butanamide

Details on test material:

- Name of test material (as cited in study report): Diacetessig - p - phenylendiamid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Test system: Rat, HanRcc:WIST (SPF)
- Rationale: Recognized by the international guidelines as a recommended test system.
- Source: RCC Ltd, Laboratory Animal Services, CH-4414 Füllinsdorf / Switzerland
- Number of animals per group: 3 females
- Total number of animals: 6 females
- Age when treated: 12 to 13 weeks
- Identification: Unique cage number and corresponding color-coded spots on the tail. Animals were marked at acclimatization start.
- 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.
- Room no.: 0105 / RCC Ltd, Füllinsdorf
- Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with ranges for room temperature 22 ± 3 °C and for relative humidity between 30-70 % (values above 70 % during cleaning process possible), automatically controlled light cycle of 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 ('Lignocel' Schill AG, CH-41 32 Muttenz/Switzerland).
- Diet: Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 25/05 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland) ad libitum. Results of analyses for contaminants are archived at RCC Ltd.
- Water: Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are ar-chived at RCC Ltd.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Polyethylene glycol 300 (PEG 300)

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 19 hours (access to water was permitted). Food was provided again 3 hours after dosing. The application volume was 10 mL/kg body weight.
Rationale: Oral administration was considered to be an appropriate application method as it is a possible route of human exposure during manufacture, handling and use of the test item.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6

Control animals:

no

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: No clinical signs were observed during the course of the study.

Gross pathology:

Congestion in the lungs was noted in one animal upon scheduled necropsy. No macroscopic findings were recorded in the remaining animals.

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 diacetessig-p-phenylendiamid 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

Executive summary:

Two groups, each of three female HanRcc:WIST (SPF) rats, were treated with Diacetessig- p-phenylendiamid by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (PEG 300) at a concentration of 0.2 g/mL and administered at a volume dosage 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 at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2 -15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2 -15.Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study period.

No clinical signs were observed during the course of the study.

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

Congestion in the lungs was noted in one animal upon scheduled necropsy. No macroscopic findings were recorded in the remaining animals.