Reaction mass of N-[3-(dimethylamino)propyl]docosanamide and N-[3-(dimethylamino)propyl]stearamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 dec 2008 - 30 jan 2009

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

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

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(dimethylamino)propyl]stearamide

EC Number:

231-609-1

EC Name:

N-[3-(dimethylamino)propyl]stearamide

Cas Number:

7651-02-7

Molecular formula:

C23H48N2O

IUPAC Name:

N-[3-(dimethylamino)propyl]octadecanamide

Constituent 2

Reference substance name:

N-[3-(dimethylamino)propyl]docosanamide

EC Number:

262-134-8

EC Name:

N-[3-(dimethylamino)propyl]docosanamide

Cas Number:

60270-33-9

Molecular formula:

C27H56N2O

IUPAC Name:

N-[3-(dimethylamino)propyl]docosanamide

Test material form:

solid: pellets

Test animals

Species:

rat

Strain:

other: HanRcc:WIST (SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

Animals: Rat, HanRcc: WIST(SPF)
Rationale: Recognized by international guidelines as a recommended test system.
Breeder: Harlan Laboratories Ltd. Laboratory Animal Services Wölferstrasse 4 / 4414 Füllinsdorf / Switzerland
Number of Animals per Group: 3 females
Total Number of Animals: 6 females
Age (when treated): 11 weeks
Body Weight Range (when treated): 178.2 g – 192.4 g
Identification: Unique cage number and corresponding color-coded spots on the tail. The 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.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Sesame oil

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 18 to 18.5 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:

6 female

Details on study design:

The dose formulations were made shortly before each dosing occasion using a magnetic stirrer, a spatula and an Ultra Turax (Janke & Kunkel, D-79219 Staufen) as homogenizers.
The test item was first reduced into a fine powder using a pestle and a mortar. Thereafter, the pulverized 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.

Statistics:

Body weights were recorded on-line.
Clinical signs were recorded on data sheets.
Mortality/viability were compiled into the RCC Tox Computer System during recording and/or recorded on data sheets.
Macroscopic findings were compiled into the RCC Tox Computer System during recording.
The RCC Tox Computer System (RCC-Tox-Lims) had been validated with respect to data collection, storage and retrievability.

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:

One hour after dosing, a slightly ruffled fur was noted in three out of six treated females and persisted up to the 5-hour observation. Otherwise, no clinical signs were observed in any animal at any observation.

Body weight:

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

Gross pathology:

No macroscopic findings were recorded at necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The median lethal dose of Genamin BAP 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 Genamin BAP by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was formulated in sesame oil 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 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.

One hour after dosing, a slightly ruffled fur was noted in three out of six treated females and

persisted up to the 5-hour observation. Otherwise, no clinical signs were observed in any animal at any observation.

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 Genamin BAP 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