Pentanediamide, N1,N5-dibutyl-2-[(2-ethyl-1-oxohexyl)amino]-, (2S)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 February 2001 - 16 March 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(2S)-N,N'-dibutyl-2-(2-ethylhexanamido)pentanediamide

EC Number:

700-664-8

Cas Number:

486455-65-6

Molecular formula:

C21H41N3O3

IUPAC Name:

(2S)-N,N'-dibutyl-2-(2-ethylhexanamido)pentanediamide

Test animals

Species:

rat

Strain:

other: HanBrl: WIST (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test Animals
Source: RCC Ltd, Biotechnology & Animal Breeding Division, CH-4414, Füllingsdorf / Switzerland
Number of animals per group: 3 males or 3 females
Total number of animals: 3 males and 3 females
Age when treated: Males: 8 weeks; Females: 10 weeks
Identification: By unique cage number and corresponding color-coded spots on the tail.
Acclimatization: Under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Husbandry
Room no.: E 16
Conditions: Standard Laboratory Conditions
Air-conditioned with 10-15 air changes per hour and continuously monitored environment with a target range for room temperature of 22 ± 3 °C, and for relative humidity between 30 and 70 % (values above 70 % during cleaning process possible), 12 hours artificial fluorescent light/12 hours dark, music during the light period.

Accommodation: Groups of three per sex in Makrolon type-4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz)
Diet: Pelleted standard Kliba 3433, batch no. 05/00, rat maintenance diet (Provimi Kliba AG, CH-4303 Kaiseraugst) available ad libitum (except for the overnight fasting period prior to intubation). Results of analyses for contaminants are archived at RCC Ltd, Itingen.
Water: Community tap water from Itingen, available ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd, Itingen.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 300

Details on oral exposure:

Test Item Preparation
The test item was placed into a glass beaker on tared balance MTLR 503-S and the vehicle (polyethylene glycol PEG 300) was added. A weight by volume dilution was prepared using a magnetic stirrer as homogenizer. Homogeneity of the test item in the vehicle was maintained during treatment.
The preparation was made shortly before each dosing.
Dose level was in terms of material as supplied by the sponsor.

Treatment
The animals received a single dose of the test item on a 2000 mg/kg body weight basis by oral gavage following fasting for approximately 16-20 hours but with free access to water. Food was provided again 3 hours after dosing.

Dose / kg body weight: 2000 mg
Application volume / kg body weight: 10 ml

Oral administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Observations
Mortality: Once daily during acclimatization period, one, two, three and five hours after test item administration on test day 1 and twice daily during days 2-15.
Body weights: On test days 1 (pre-administration), 8 and 15.
Clinical signs: Each animal was examined for changes in appearance and behaviour once daily during the acclimatization phase. One, two, three and five hours after test item administration on test day 1, and once daily during days 2-15. All abnormalities were recorded.

Necropsy
At the end of the observation period all animals were sacrificed by intraperitoneal injection of NARCOREN (Rhône Mérieux GmbH, D-88471 Laupheim) at a dose of at least 2.0 ml/kg body weight (equivalent to at least 320 mg sodium pentobarbitone/kg body weight). The animals were examined macroscopically and all abnormalities were recorded. Thereafter, they were discarded.

Statistics:

No statistical analysis was used.

Results and discussion

Effect levels

Sex:

male/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 clinic signs were evident during the observation period.

Gross pathology:

No macroscopic findings were observed at necropsy.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

The median lethal dose of the test material after single oral administration to rats of both sexes, observed over a period of 14 days is:
LD50 (rat): greater than 2000 mg/kg body weight

Executive summary:

In an acute oral toxicity study (793631) according to EU Test Method B.1 tris, one group of three male or three female HanBrl: WIST (SPF) rats were treated with the test material at 2000 mg/kg by oral gavage. The test item was suspended in vehicle (polyethylene glycol PEG 300) at a concentration of 0.2g/ml and administered at a volume of 10 ml/kg. The animals were examined for clinical signs four times during test day 1 and once daily during test days 2-15. Mortality/viability was recorded together with clinical signs at the same time intervals on test day 1 and then twice daily on test 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.

There were no clinical signs noted during observation period.

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

No macroscopic findings were observed at necropsy.

The median lethal dose of the test material after single oral administration to rats of both sexes, observed over a period of 14 days is:

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