Amides, coco, N-[3-(dimethylamino)propyl], N-oxides

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From October 20, 1999 to November 24, 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

March 1996

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Amides, coco, N-[3-(dimethylamino)propyl], N-oxides

EC Number:

268-938-5

EC Name:

Amides, coco, N-[3-(dimethylamino)propyl], N-oxides

Cas Number:

68155-09-9

Molecular formula:

Unspecified

IUPAC Name:

Amides, coco, N-[3-(dimethylamino)propyl], N-oxides

Details on test material:

- Purity: approximately 81%
- Lot/batch No.: 876 TK
- Physical state: off white paste
- Storage condition of test material: room temperature, in the dark.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source: Stepan Company, Illinois, USA
- Batch No.of test material: 876 TK
- Date received: 10 May 1999
- Description: white paste

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature in the dark

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Freshly prepared as a solution in distilled water
- Final dilution of a dissolved solid: The dose levels were selected using a correction factor based on the purity of the supplied test material, to ensure that the animals received equivalent to 200 or 2000 mg/kg of pure test material

FORM AS APPLIED IN THE TEST: solution

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: eight to twelve weeks old
- Weight at study initiation: males weighed 228 to 236 g, and the females 201 to 236 g
- Fasting period before study: overnight immediately before dosing
- Housing: in groups of three by sex in solid-floor polypropylene cages furnished with wood flakes
- Diet (e.g. ad libitum): ad libitum with the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): The rate of air exchange was approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): cycles of twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 217.4 mg/ml and 21.8 mg/ml
- Amount of vehicle (if gavage): 10 ml

DOSAGE PREPARATION: The test material solutions were prepared using a correction factor based on the purity of the test substance to ensure that the animals received 2000 and 200 mg/kg of the pure test material

MAXIMUM DOSE VOLUME APPLIED: 10 mL

CLASS METHOD
- Rationale for the selection of the starting dose: Using all available information, 2174 mg/kg bodyweight was selected as the starting dose. (This dose level was selected using a correction factor based on the purity of the supplied test material, to ensure that the animals received a dose equivalent to 2000 mg/kg bodyweight of pure test material).

OTHER:
- animals were dosed once only by gavage

Doses:

2174 mg/kg (equivalent to 2000 mg pure test material/kg) and 218 mg/kg (equivalent to 200 mg pure test material/kg)

No. of animals per sex per dose:

2174 mg/kg: a group of 3 female rats.
218 mg/kg: 6 rats, one group of 3 females and one group of 3 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Observation: Death or overt signs of toxicity were checked at 1/2, 1, 2, and four hours after dosing and subsequently once daily
- Frequency of observations and weighing: Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 500 - <= 1 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Pure test substance

Mortality:

Two animals treated with 2174 mg/kg were found dead one or two days after dosing. There were no deaths noted at a dose level of 218 mg/kg.

Clinical signs:

other: Clinical signs in animals treated with 2174 mg/kg were hunched posture, diarrhoea and increased salivation with incidents of pallor of the extremities, emaciation, lethargy, pilo-erection, decreased respiratory rate, laboured respiration, red/brown staini

Gross pathology:

Necropsy results of animals that died during the study (treated with 2174 mg/kg) were haemorrhagic lungs, dark liver, dark kidneys, haemorragic gastric mucosa, sloughing and/or haemorrhage of the non-glandular epithelium of the stomach and haemorrhagic small and large intestines. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Any other information on results incl. tables

Mortality data

Dose level [mg/kg]	Animal number and sex	Number of animals treated	Deaths during day of dosing (hours)				Effects noted after dosing (days)
			1/2	1	2	4	1	2	3	4	5	6	7	8-14	Deaths
2174	female	3	0	0	0	0	1	1	0	0	0	0	0	0	2/3
218	female	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3
	male	3	0	0	0	0	0	0	0	0	0	0	0	0	0/3

Individual Clinical Observations

Dose level mg/kg	Animal Nº and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
2174		1/2	1	2	4	1	2	3	4	5	6	7	18	9	10	11	12	13	14
	1-0 Female	H	H	HD	HD	HPD Ss	HP	H	H
	1-1 Female	HS	HS	HSD	HSD	X
	1-2 Female	HS	HS	HSD	HSD	H P Em Ss Rd RL Wt E	X

D: diarrhea                                                               E: pallor of extremities

Em: emaciation                                                         H: hunched posture

L: lethargy                                                               P: pilo-erection

Rd: decreased respiratory rate                                RL: labored respiration

S: increased salivation                                              Ss: red/brown stainig around snout

Wt: tiptoe gait                                                          X: animal death

 

No clinical observations were noted at the dose of 218 mg/kg.

 

Body weights

Only the animals that died during the study showed a loss of weight

 

Dose Level mg/kg	Animal Nº and sex	Body weight (g) at day			Body weight (g) at
2174		0	7	14	Death
	1-0 Female	204	243	246
	1-0 Female	201			175
	1-0 Female	207			170

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of the test substance in Sprague-Dawley rats was in the range of 500 – 1000 mg/kg of pure test substance.

Executive summary:

The Acute Oral toxicity – Acute Toxic Class method study for the test substance was performed in Sprague-Dawley CD strain rats. A stepwise procedure was used; a group of 3 females was treated with a dose of 2174 mg/kg (equivalent to 2000 mg of pure test material/kg) and 2 groups (3 females and 3 males) were treated with a dose of 218 mg/kg (equivalent to 200 mg of pure test material /kg). The test substance was administered as a solution in distilled water. An oral single dose of 10 ml/kg was given by gavage.

Clinical observations were made at 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for up to 14 days. Individual body weights were recorded prior to dosing and 7 and 14 days after treatment or at death. All animals including those that died during the study were subjected to gross pathological observations. Two animals treated with 2174 mg/kg died. No mortalities were noted in animals treated with 218 mg/kg. The acute oral LD50 of the test substance in Sprague-Dawley rats was in the range of 500 – 1000 mg/kg of pure test substance.