N-[3-(dimethylamino)propyl]stearamide monoacetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2014-10-17 to 2015-02-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(dimethylamino)propyl]stearamide monoacetate

EC Number:

236-291-8

EC Name:

N-[3-(dimethylamino)propyl]stearamide monoacetate

Cas Number:

13282-70-7

Molecular formula:

C23H48N2O.C2H4O2

IUPAC Name:

N-[3-(dimethylamino)propyl]stearamide monoacetate

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

CRL

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable): based on consistently acceptable health status and on extensive experience with the strain at DuPont Haskell.
- Source: Charles River Laboratories International, Inc., Raleigh, North Carolina, U.S.A.
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Rationale for use of males (if applicable):n/a
- Age at study initiation: 8-11 weeks old on the day of dosing.
- Weight at study initiation: n/a
- Fasting period before study: 16-18 hours prior to dosing.
- Housing:individually in solid-bottom caging with bedding and appropriate species- specific enrichment.
- Historical data:n/a
- Diet (e.g. ad libitum): PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002, ad libitum.
- Water (e.g. ad libitum):ad libitum except as noted in section E. Dosing.
- Acclimation period:6-day quarantine period.
- Microbiological status when known: Water samples are analyzed for total bacterial counts, and the presence of coliforms, lead, and other contaminants. Samples from freshly washed cages and cage racks are analyzed to ensure adequate sanitation by the cagewashers.
- Method of randomisation in assigning animals to test and control groups: A software package (AOT425StatPgm)a was used to determine the dose progression.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26°C
- Humidity (%): 30-70%
- Air changes (per hr): n/a
- Photoperiod (hrs dark / hrs light): Animal rooms were artificially illuminated (fluorescent light) on an approximate 12-hour light/dark cycle.

IN-LIFE DATES: From:21 October 2014 To: 3 December 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

0.1% Tween 80 (V/V) in deionized water

Details on oral exposure:

VEHICLE
- Concentration in vehicle:(1:1)
- Amount of vehicle (if gavage):0.1%
- Justification for choice of vehicle:n/a
- Lot/batch no. (if required): n/a
- Purity: n/a

Doses:

175, 550, 1750, 5000, and 2000 mg/kg.
The rats were dosed at a volume of 10, 17.5, 20, or 40 mL per kg of body weight.

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:daily observation and weighted on days -1,1,8 and 15 or on the day of the sacrifice.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:n/a

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 403 mg/kg bw

Based on:

test mat.

Mortality:

All animals dosed at 5000 or 2000 mg/kg died within a day after dosing

Clinical signs:

diarrhoea

Body weight:

other body weight observations

Gross pathology:

Gross findings were present in 4 female rats; 2 found dead and 2 sacrificed prior to scheduled sacrifice. The 2 found dead rats were administered 2000 mg/kg and had brown/green staining of the skin of the perineum. Of the 2 rats sacrificed prior to scheduled sacrifice, one was administered 2000 mg/kg and had brown staining about the perineum, yellow/clear fluid in the small intestine and cecum as well as whole body thinness (presumed dehydration). The other rat was administered 5000 mg/kg and had brown staining of the skin of the perineum. These observations are non-specific and not indicative of target organ toxicity. No other gross findings were observed.

Other findings:

- 5000 or 2000 mg/kg groups, preceding death.:
cold to touch, dehydration, eyelid ptosis, hunched posture, hypoactive, moribund status, decreased muscle tone, pale, high posture, prostrate, soiled skin or fur, and wet fur.
- At 1750 mg/kg:
diarrhea, soiled skin or fur, and wet fur between test days 2 and 3.
- At 550 mg/kg:
diarrhea and soiled skin or fur in 2/3 animals between test days 1 and 3.

Any other information on results incl. tables

Test Sequence	Group ID	Dose (mg/kg)	Short-term Result	Long-term Result
1	1	175	O	O
2	2	550	O	O
3	3	1750	O	O
4	4	5000	X	X
5	5	2000	X	X
6	6	550	O	O
7	7	2000	X	X
8	8	550	O	O
9	9	2000	X	X

X Died

O Survived

 

Summary of Long-Term Results

 

Dose (mg/kg)	O	X	Total
175	1	0	1
550	3	0	3
1750	1	0	1
2000	0	3	3
5000	0	1	1
All Doses	5	4	9

 Statistical Estimate based on long term outcomes: the LD50 is 1403 mg/kg.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study, the oral LD50 for H-31339 was 1403 mg/kg for female rats.
According to the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS), Fifth revised edition 2013, H-31339 is classified in Category 4.

Executive summary:

H-31139 was administered by oral gavage to fasted female rats at a dose of 175, 550, 1750, 5000, or 2000 mg/kg. The rats were dosed one at a time at approximately 48-hour intervals. All rats were observed for mortality, body weight effects, and clinical signs for 14 days after dosing. The rats were necropsied to detect grossly observable evidence of organ or tissue damage.

All animals dosed at 5000 or 2000 mg/kg died within a day after dosing; clinical abnormalities preceding death included abnormal gait, cold to touch, dehydration, diarrhea, eyelid ptosis, hunched posture, hypoactive, moribund status, decreased muscle tone, pallor, high posture, prostrate, salivation, soiled skin or fur, and wet fur. At 1750 mg/kg, there were no incidents of mortality or overall body weight losses; clinical abnormalities included diarrhea, soiled skin or fur, and wet fur between test days 2 and 3. At 550 mg/kg, there were no incidents of mortality or overall body weight losses; clinical abnormalities included diarrhea and soiled skin or fur in 2/3 animals between test days 1 and 3. At 175 mg/kg there were no incidents of mortality, overall body weight losses, or clinical abnormalities.

Gross findings were present in 4 female rats; 2 found dead and 2 sacrificed prior to scheduled sacrifice. The 2 found dead rats were administered 2000 mg/kg and had brown/green staining of the skin of the perineum. Of the 2 rats sacrificed prior to scheduled sacrifice, one was administered 2000 mg/kg and had brown staining about the perineum, yellow/clear fluid in the small intestine and cecum as well as whole body thinness (presumed dehydration). The other rat was administered 5000 mg/kg and had brown staining of the skin of the perineum. These observations are non-specific and not indicative of target organ toxicity. No other gross findings were observed.

Under the conditions of this study, the oral LD50 for H-31339 was 1403 mg/kg for female rats.

In accordance with the provisions of Directive 67/548/EEC amended by COMMISSION DIRECTIVE 2001/59/EC of 6 August 2001, Annex VI, H-31339 is assigned the symbol “Xn” and the risk phrase “Harmful if swallowed.”

According to the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS), Fifth revised edition 2013, H-31339 is classified in Category 4.