N-[3-(dimethylamino)propyl]dodecanamide N-oxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12 May - 17 Jun 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

adopted in 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

adopted in 2008

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

adopted in 2002

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Appendix to Director General Notification, No. 12-Nousan-8147. Agricultural Production Bureau, Ministry of Agriculture, Forestry and Fisheries of Japan (JMAFF)

Version / remarks:

adopted in 2000

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(dimethylamino)propyl]dodecanamide N-oxide

EC Number:

263-218-7

EC Name:

N-[3-(dimethylamino)propyl]dodecanamide N-oxide

Cas Number:

61792-31-2

Molecular formula:

C17H36N2O2

IUPAC Name:

N-[3-(dimethylamino)propyl]dodecanamide N-oxide

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 9 - 10 weeks
- Weight at study initiation: 168 – 192 g
- Fasting period before study: 20 h
- Housing: Up to 5/sex in polycarbonate cages (Makrolon MIV type, 18 cm height) containing sterilised wooden fibers as bedding material and enriched with paper.
- Diet: pelleted rodent diet SM R/M-Z (SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: municipal tap water, ad libitum
- Acclimation period: at least 5 days
- Microbiological status when known: SPF quality

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24 (21 °C daily mean temperature)
- Humidity (%): 41 - 69
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

- Rationale for the selection of the starting dose: The dose level was selected based on the results of a pilot study in which a single female rat was dosed at 2000 mg/kg bw. The female was found dead on Day 2, showing ante mortem clinical signs and macroscopic abnormalities at gross necropsy (for details please refer to “Results and discussion, Preliminary study”). A second pilot animal was dosed at 300 mg/kg bw and no mortality was observed. Therefore the main study was conducted at 300 mg/kg bw.

Doses:

Pilot study: 2000 mg/kg bw (step 1) and 300 mg/kg bw (step 2)
Main study: 300 mg/kg bw

No. of animals per sex per dose:

Pilot study: 1 female per step (2 steps)
Main study: 4 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter.
- Frequency of weighing: Animals were weighed individually on Day 1 (pre-dose), 8 and 15. A fasted weight was recorded on the day of dosing. Terminal body weights were collected for animals found dead or moribund animals euthanised after Day 1.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed.

Results and discussion

Preliminary study:

In a pilot study a single female rat was dosed at 2000 mg/kg bw at the first step. The rat was found dead on Day 2 and prior to death showed clinical signs including lethargy, hunched posture, piloerection, decreased locomotor activity, and shallow respiration. Advanced autolysis was found in this animal at macroscopic post mortem examination. In a second step one female rat was dosed at 300 mg/kg bw. No clinical signs of toxicity were observed and no mortality occurred. Therefore the main study was conducted at 300 mg/kg bw.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

300 - 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Pilot study:
300 mg/kg bw: 0/1 females died
2000 mg/kg bw: 1/1 females (at 2 days post dose)
Main study: No mortality occured during the study period.

Clinical signs:

other: Pilot study: 300 mg/kg bw: No clinical signs of toxicity were observed up to the end of the 14-day observation period. 2000 mg/kg bw: 1/1 females showed lethargy, hunched posture, piloerection, decreased locomotor activity, and shallow respiration. The e

Gross pathology:

Necropsy and histopathological examination revealed no substance-related findings.

Applicant's summary and conclusion

Interpretation of results:

other: Acute Oral 4, H302 according to Regulation (EC) No. 1272/2008

Conclusions:

In this acute oral toxicity study in rats a test item dose of 2000 mg/kg bw induced hunched posture in all rats, which was was fully reversible within 48 hours post-administration. The LD50 value was determined to be between 300 - 2000 mg/kg bw.