N-[3-(dimethylamino)propyl]docosanamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-12-02 to 2008-12-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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:

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

Version / remarks:

May 2008

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 17 December 2001

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-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %)

IUPAC Name:

N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %)

Details on test material:

- Name of test material: N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %)
- Physical state: solid
- Analytical purity: 99%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 11 weeks
- Body weight range: 178.2-192.5 g
- Fasting period before study: 18 to 18.5 hours prior to dosing and until approximately 3 hours after administration of the test substance (access to water was permitted)
- Housing: 3/cage
- Diet (e.g. ad libitum): pelleted rodent diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light):12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: sesame oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/L
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: test item not well soluble in water
- Lot/batch no. (if required): 067K0069
- Source: Sigma-Aldrich
-Stability of the vehicle: Stable under storage conditions (at room temperature, light proteced); expiration date: 08/2012

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): The test item was reduced into a fine powder, then the vehicle was added and the formulation was after that homogenized using a magnetic stirrer, a spatula and an Ultra Turax.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: mortality: first 30 min, 1 ,2, 3 and 5 hours, therafter twice daily; clinical signs: first 30 min, 1 ,2, 3 and 5 hours, daily thereafter
- Frequency of weighing: On test days 1, 8 and 15
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: no mortalities

Mortality:

No deaths occured during the study

Clinical signs:

other: 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 timepoint.

Gross pathology:

No macroscopic findings were recorded at necropsy

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %) in female rats was > 2000 mg/kg bw.

Executive summary:

In an acute oral toxicity study according to OECD guideline 423, adopted 17 December 2001 and EU method B.1 tris, May 2008, 6 female, fasted, 8-11 weeks old Wistar strain rats were given a single oral dose of N-[3-(dimethylamino)propyl]stearamide (C18) and N-[3-(dimethylamino)propyl]docosanamide (C22) 50:50 (w/w %) in sesame oil by gavage at the limit dose of 2000 mg/kg bw and observed for 14 days.

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 timepoint. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy.

Oral LD50 (rat, females) > 2000  mg/kg bw