Registration Dossier

Diss Factsheets

Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.

REACH

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

EC number: 268-938-5 | CAS number: 68155-09-9

Life Cycle description
Uses advised against

Toxicological information

Endpoint summary

Administrative data

Description of key information

Oral:

LD50 of between 500 and 1000 mg/kg.

OECD 423, GLP (Stepan, 2000), Sprague-Dawley rats exposed to 200 mg/kg (only females) and 2000 mg/kg (males and females). Two animals treated with 2000 mg/kg were found dead one or two days after dosing. Necropsy results revealed dark liver and dark kidneys in the 2000 mg/kg group.

Dermal:

LD50 greater than 2000 mg/kg

OECD 402, GLP (Stepan, 2000), 5 Sprague-Dawley rats exposed to 2000 mg/kg. No observed mortality. In four animals, a slight brown discoloration was observed.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

March 1996

Deviations:

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:

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

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.

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:

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.

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.

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)
Dose level [mg/kg]	Animal number and sex	Number of animals treated	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
218	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

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.

Endpoint conclusion

Endpoint conclusion:: adverse effect observed
Dose descriptor:: discriminating dose
Value:: 500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:: no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:: acute toxicity: dermal
Type of information:: experimental study
Adequacy of study:: key study
Study period:: From October 20, 1999 to November 3, 1999
Reliability:: 1 (reliable without restriction)
Rationale for reliability incl. deficiencies:: guideline study
Qualifier:: according to guideline
Guideline:: OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:: Feb 1987
Deviations:: no
Qualifier:: according to guideline
Guideline:: EU Method B.3 (Acute Toxicity (Dermal))
Deviations:: no
GLP compliance:: yes (incl. QA statement)
Test type:: standard acute method
Limit test:: yes
Specific details on test material used for the study:: SOURCE OF TEST MATERIAL
- Source:
- Batch No.of test material: 876 TK
- Date received: 10 May 1999
- Purity: 92%
- Physical appearance: 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: The test material was used as supplied. It was weighed out according to the animals individual body weight.
Species:: rat
Strain:: Sprague-Dawley
Remarks:: Crl: CD (SD) IGS BR
Sex:: male/female
Details on test animals or test system and environmental conditions:: TEST ANIMALS
- Source: Charles River (UK)
- Age at study initiation: approximately eight to twelve weeks old
- Weight at study initiation: males 206 to 232 g, and the females 214 to 225 g.
- Housing: in suspended polypropylene cages furnished with wood flakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 ºC
- Humidity (%): 30-70 %
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light and twelve hours darkness
Type of coverage:: semiocclusive
Vehicle:: unchanged (no vehicle)
Details on dermal exposure:: REMOVAL OF TEST SUBSTANCE
- Washing (if done): with cotton wool moistened with distilled water to remove any residual test material.
- Time after start of exposure: After the 24-hour contact period

TEST SITE
- Area of exposure: Back and flank of animals
- % coverage: approximating to 10% of the total body surface area.
- Type of wrap if used: Surgical gauze and self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: Residual test substance was wiped off with cotton wool moistened with distilled water
- Time after start of exposure: After a 24-hour contact period

TEST MATERIAL
- Amount applied: not specified
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE
- No vehicle used. The undiluted test substance was used.
Duration of exposure:: 24-hours
Doses:: 2174 mg/kg (equivalent to 2000 mg/kg bodyweight of pure test material).
No. of animals per sex per dose:: Ten animals (five males and five females)
Control animals:: no
Details on study design:: - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Scoring system: Scale from Draize J H (1977)
Statistics:: Mortality data was used to estimate the acute dermal median lethal dose (LD50) of the test substance
Sex:: male/female
Dose descriptor:: LD50
Effect level:: > 2 174 mg/kg bw
Based on:: test mat.
Remarks on result:: other: The dose 2174 mg/kg is equivalent to 2000 mg/kg bodyweight of pure test material
Mortality:: There were no deaths.
Clinical signs:: other: No signs of systemic toxicity were noted during the study. Very slight to well-defined erythema was noted at the treatment sites of all animals one and two days after dosing, in nine animals three days after dosing and in four animals four days after dosi
Gross pathology:: No abnormalities were noted at necropsy.
Other findings:: Residual test material was noted at the treatment sites of all animals during the study and prevented accurate evaluation of oedema in two males one to five days after dosing.
One female showed body weight loss during the first week andd expected gain in body weight during the second week. All other animlas showed normal body weights.
Interpretation of results:: GHS criteria not met
Conclusions:: The acute dermal median lethal dose (LD50) of the test substance in the Sprague-Dawley CD strain rat was found to be greater than 2174 mg/kg bodyweight (equivalent to 2000 mg/kg bodyweight of pure test material).
Executive summary:: The Acute Dermal Toxicity assay for the test substance was performed in Sprague-Dawley CD rats. One female group and one male group, of 5 animals each one, were treated with a single dose of 2174 mg/kg bodyweight, equivalent to 2000 mg/kg bodyweight of pure test material (Limit test). The test material was applied uniformly to an area of shorn skin (approximating to 10% of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water. Clinical observation was conducted at 1/2,1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Body weight was controlled before the administration, on day 0 and on days 7 and 14 after the administration. All animals were subjected to gross necropsy. No test substance related effects were noted from clinical observations or post-mortem examination. The acute dermal median lethal dose (LD50) of the test substance in the Sprague-Dawley CD strain rat was found to be greater than 2174 mg/kg bodyweight (equivalent to 2000 mg/kg bodyweight of pure test material).

Endpoint conclusion

Endpoint conclusion:: no adverse effect observed

Additional information

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 calculated in the range of 500 – 1000 mg/kg of pure test substance.

The Acute Dermal Toxicity assay for the test substance was performed in Sprague-Dawley CD rats. One female group and one male group, of 5 animals each one, were treated with a single dose of2174 mg/kg bodyweight, equivalent to 2000 mg/kg bodyweight of pure test material(Limit test).The test material was applieduniformly to an area of shorn skin (approximating to 10% of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water.Clinical observation was conducted at 1/2,1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.Body weight was controlled before the administration, on day 0 and on days 7 and 14 after the administration. All animals were subjected to gross necropsy.No test substance related effects were noted from clinical observations or post-mortem examination.The acute dermal median lethal dose (LD50) of the test substance in the Sprague-Dawley CD strain rat was found to be greater than 2174 mg/kg bodyweight (equivalent to 2000 mg/kg bodyweight of pure test material).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for the purpose of classification. Based on the criteria laid down in Regulation (EC) No.1272/2008, as amended for the second time in Directive EC 286/2011, the test substance is classified for acute toxicity with category 4 (H302).

Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

Doselevel mg/kg	Animal Number and Sex	Bodyweight (g) atDay			Bodyweight Gain (g) During Week
		0	7	14	1	2
2174	1-0 Male	206	238	286	32	48
	1-1 Male	228	285	336	57	51
	1-2 Male	232	280	345	48	65
	1-3Male	220	257	312	37	55
	1-4 Male	215	201	322	46	61
	2-0 Female	214	215	234	1	19
	2-1 Female	220	225	236	5	11
	2-2 Female	225	220	245	-5	25
	2-3 Female	224	235	265	11	30
	2-4 Female	225	226	250	1	24