Registration Dossier

Administrative data

Description of key information

Oral: Two key studies: Tests according to OECD guideline 420 and EU method B.1 bis. GLP study. LD50 300-2000 mg active ingredient/kg bw. 
Dermal: Key study: Read-across from experimental data on the analogue CAS No. 68155-09-9. Test according to OECD guideline 402 and EU method B.3. GLP study. LD50 >2000 mg/kg bw.

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 3 March 2011 to March 29, 2011.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: EU Method and GLP study.
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd., Oxon, UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 180-186 g
- Fasting period before study: overnight fast immediately before dosing.
- Housing: in groups of up to four in suspended solid-flood polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum (with the exception of the 3-4 hours fast period after dosing). 2014 Teklad Global Rodent diet.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25ºC
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15 changes / hour
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light (06:00 to 18:00 h).
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
6.13 ml/kg (6061 mg/kg bw dose level, equivalent to 2000 mg active ingredient/kg bw)
0.93 ml/kg (910 mg/kg bw dose level, equivalent to 300 mg active ingredient/kg bw)

Doses:
6061 mg/kg of the test item (equivalent to 2000 mg active ingredient/kg bw)
910 mg/kg of the test item (equivalent to 300 mg active ingredient/kg bw)
No. of animals per sex per dose:
Group 1 (2000 mg active ingredient/kg bw): 1
Group 2 (300 mg active ingredient/kg bw): 5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were made ½, 1, 2 and 4 hours after dosing and then daily for up to fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes, by cervical dislocation. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Sex:
female
Dose descriptor:
LD50
Effect level:
910 - 6 061 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Equivalent to 300-2000 mg active ingredient/kg bw
Mortality:
The animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw) was found dead one day after dosing. There were no deaths at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw).
Clinical signs:
Exophthalmos and hunched posture were noted in the animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw). Signs of systemic toxicity noted in the initial animal treated at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw) were hunched posture, noisy respiration and pilo-erection. There were no signs of systemic toxicity noted in the additional four animals treated at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw).
Body weight:
All animals showed expected gains in bodyweight.
Gross pathology:
Abnormalities noted at necropsy of the animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw), that died during the study, were dark liver, dark kidneys, gaseous distension and dark brown coloured liquid present in the stomach and haemorrhage of the gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test item in rats was estimated to be in the range of 910-6061 mg/kg bw (equivalent to 300-2000 mg active ingredient/kg bw).
Executive summary:

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with OECD Guideline 420 “Acute Oral Toxicity - Fixed Dose Method” and EU Method B1 bis Acute Toxicity (Oral).

Following a sighting test at dose levels of 6061 mg/kg and 910 mg/kg (equivalent to 2000 and 300 mg active ingredient/kg bw, respectively), a further group of four fasted females was given a single oral dose of test item at a dose level of 910 mg/kg bw (equivalent to 300 mg active ingredient/kg bw). Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. The animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw) was found dead one day after dosing. There were no deaths at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw). The clinical observations noted were exophthalmos and hunched posture (at a dose of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw)). Signs of systemic toxicity noted in the initial animal treated at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw) were hunched posture, noisy respiration and pilo-erection. No signs of systemic toxicity were noted in the additional four animals treated at a dose level of 910 mg/kg (equivalent to 300 mg active ingredient/kg bw). Surviving animals showed expected gains in bodyweight. Abnormalities were noted at necropsy of the animal treated at a dose level of 6061 mg/kg (equivalent to 2000 mg active ingredient/kg bw), that died during the study. No abnormalities were noted at necropsy of animals that were killed at the end of the study. The acute oral median lethal dose (LD50) of the test item in rat was estimated to be in the range 910-6061 mg/kg bw (equivalent to 300-2000 mg active ingredient/kg bw).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
The key studies are GLP compliant and of high quality (Klimisch score = 1).

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The analogue which shares the same functional group also has comparable values for the relevant molecular properties.
Reason / purpose for cross-reference:
reference to other study
Principles of method if other than guideline:
Read-across approach from experimental data on an analogue.
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
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

The analogue CAS No. 68155-09-9 which shares the same functional groups with the substance Amides, C12-C14 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides, also has comparable values for the relevant molecular properties.

 

Cocamidopropylamine Oxide (CAS 68155-09-9) where R=C8-C18, is a tertiary amine oxide where RCO- represents the fatty acids from coconut oil. Coconut oil contains predominantly medium chain triglycerides with roughly 92% saturated fatty acids, 6% monounsaturated fatty acids, and 2% polyunsaturated fatty acids. Of the saturated fatty acids, coconut oil is primarily 44.6% lauric acid, 16.8% myristic acid, 8.2% palmitic acid, 8% caprylic acid, and other seven different saturated fatty acids in small amount. Its only monounsaturated fatty acid is oleic acid while its only polyunsaturated fatty acid is linoleic acid.

 

Therefore, the source chemical and the target chemical share the following functional groups:

a.- N-Oxide functionality

b.- Amide group

 

For the source substance, in the chemical structure, the R is substituted by C8-C18 and for the target substance the R is substituted by C12-C14.

 

Based on company experimental data (reported under the endpoint record Acute toxicity: dermal_47) on the analogue CAS No. 68155-09-9, the read-across approach is applied and the dermal LD50 for the substance Amides, C12-14 (even numbered), N-[3-(dimethylamino)propyl], N'-oxides is greater than 2000 mg/kg bw.

DATA MATRIX read-across (any other information on results, including tables).

CAS Number

 

Source chemical

68155-09-9

Target chemical

 

CHEMICAL NAME

 

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

Amides, C12-C14 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides

PHYSICO-CHEMICAL DATA

 

Melting Point

Experimental results:

292 ± 0.5 K to 399 ± 0.5 K

Experimental results:

104.3 -

 

 

Boiling Point

Experimental results:

Decomposes from approximately 403 ± 0.5 K at 100.92 kPa prior to any boiling.

 

Experimental results:

The substance decomposes before boiling.

 

pKa

No data

 

Estimated data:

pka = 15.91 ±(most acidic temperature)

pka = 4.7 ±(most basic temperature)

 

Partition Coefficient

(log Kow)

No data

Experimental results:

-0.06

    

Water solubility

 

Experimental results:

Miscible in all proportions with water at 20.0 ± 

 

Experimental results:

346.9 ± 1.7 g/l at 20.0 ±

 

Vapour pressure

Experimental results:

< 3.3 x 10-4Pa at

 

Experimental results:

Read-across

< 3.-4Pa at

ENVIRONMENTAL FATE and PATHWAY

 

Aerobic Biodegradation

 

Experimental results:

Readily biodegradable 

 

Experimental results:

Readily biodegradable 

 

ENVIRONMENTAL TOXICITY

 

Acute Toxicity to Fish

Experimental data:

Key study:

LC50 (96hr): 0.75 mg/l

 

Experimental data:

Key study:

LC50 (96 h) = 18 mg/l

 

Acute Toxicity to Aquatic Invertebrates

Experimental data:

Key study:

EC50 (48hr): 0.96 mg/l

 

Experimental data:

Key study:

EC50 (48 h) = 16 mg/l

Toxicity to Aquatic algae and cyanobacteria

 

Experimental data:

Key study:

EC50 (72hr): 4.5 mg/l

 

Experimental data: 

Key study:

EC50 (72 h) = 3.4 mg /l

MAMMALIAN TOXICITY

 

Acute Toxicity: Oral

Experimental data:

Key study:

LD50 = 500 – 1000 mg/kg

 

Experimental data:

Key study

LD50 = 300-2000 mg/kg

Key study

LD50 > 660 mg/kg

 

Acute Toxicity: Dermal

Experimental data:

Key study:

LD50 > 2000 mg/kg

Experimental data:

Read-across

LD50 > 2000 mg/kg

 

Skin irritation

Experimental data:

Key study:

The substance is classified as irritating according to Directive 67/548/EEC. However, based on the scores, the substance is not classified according to CLP Regulation.

 

Since the tested substance had a purity/concentration of 79% and since no data is available on the pure substance, taking into account the worst case, the proposal is to classify the substance as a Skin Irritant according to CLP Regulation.

 

Experimental data:

Read-across

Since the tested substance had a purity/concentration of 79% and since no data is available on the pure substance, taking into account the worst case, the proposal is to classify the substance as a Skin Irritant according to CLP Regulation.

 

Eye irritation

 

Experimental data:

Key study:

Irritating

 

Experimental data:

Read-across

Irritating

 

 

Skin sensitisation

 

 

Experimental data:

Key study:

Non-sensitiser

 

Experimental data:

Read-across

Non-sensitiser

 

 

Repeated Dose Toxicity

Experimental data: Key study:    

 

NOEL = 15 mg/kg/day                       

 

Experimental data:

Read-across

NOAEL (90 d) = 50 mg/kg/day

NOEL (28 d) = 15 mg/kg/day  

 

Genetic Toxicity in vitro

 

Gene mutation in bacteria

Experimental results: Key study:

                            

Non- mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA. 

Experimental results: 

Read-across  

 

Non- mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA. 

Chromosomal aberrations

Experimental results: Key study:

 

The substance did not induce chromosomal aberrations.

                            

 

Experimental results: 

Read-across

 

The substance did not induce chromosomal aberrations.

 

Gene mutation in mammalian cells

Experimental results: Key study:

 

The substance did not induce any toxicologically significant increases in the mutant frequency at the TK +/- locus in L5178Y cells and is therefore considered to be non-mutagenic.

 

Experimental results: 

Read-across

 

The substance did not induce any toxicologically significant increases in the mutant frequency at the TK +/- locus in L5178Y cells and is therefore considered to be non-mutagenic.

 

Toxicity to reproduction

 

Experimental results: Key study: Reproduction/Developmental toxicity screening test

The NOEL for both systemic and reproductive toxicity was considered to be 100 mg/kg/day (highest tested dose).

Experimental results: 

Read-across

 

The NOEL for both systemic and reproductive toxicity was considered to be 100 mg/kg/day.

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) was found to be greater than 2174 mg/kg bodyweight (equivalent to 2000 mg/kg bodyweight of pure test material).
Executive summary:

The analogue CAS No. 68155-09-9 which shares the same functional group with the substance Amides, C12-14 (even numbered), N-[3-(dimethylamino)propyl], N'-oxides, also has comparable values for the relevant molecular properties.

 

Based on company experimental data (reported under the endpoint record Acute toxicity: dermal_47) on the analogue CAS No. 68155-09-9, the read-across approach is applied and the dermal LD50 for the substance Amides, C12-14 (even numbered), N-[3-(dimethylamino)propyl], N'-oxides is greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The key study is GLP compliant and of high quality (Klimisch score = 1).

Additional information

Oral: Key study: Test according to OECD guideline 420 and EU method B.1 bis. GLP study.

LD50 300-2000 mg active ingredient/kg bw.

Oral: Key study: Test according to OECD guideline 420 and EU method B.1 bis. GLP study.

LD50 > 660 mg active ingredient/kg bw.

Oral: supporting study: Read-across from experimental data on the analogue CAS No. 68155-09-9. Test according to OECD guideline 423. GLP study.

LD50 between 500 -1000 mg/kg bw

Dermal: Key study: Read-across from experimental data on the analogue CAS No. 68155-09-9. Test according to OECD guideline 402 and EU method B.3.

LD50 > 2000 mg/kg bw.

Inhalation: In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted since the substance is manufactured and commercialised as a water solution and the vapour pressure of the substance is low.

The analogue CAS No. 68155-09-9 which shares the same functional groups with the substance Amides, C12-C14 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides, also has comparable values for the relevant molecular properties.

 

Cocamidopropylamine Oxide (CAS 68155-09-9) where R=C8-C18, is a tertiary amine oxide where RCO- represents the fatty acids from coconut oil. Coconut oil contains predominantly medium chain triglycerides with roughly 92% saturated fatty acids, 6% monounsaturated fatty acids, and 2% polyunsaturated fatty acids. Of the saturated fatty acids, coconut oil is primarily 44.6% lauric acid, 16.8% myristic acid, 8.2% palmitic acid, 8% caprylic acid, and other seven different saturated fatty acids in small amount. Its only monounsaturated fatty acid is oleic acid while its only polyunsaturated fatty acid is linoleic acid.

 

Therefore, the source chemical and the target chemical share the following functional groups:

a.- N-Oxide functionality

b.- Amide group

 

For the source substance, in the chemical structure, the R is substituted by C8-C18 and for the target substance the R is substituted by C12-C14.


Justification for selection of acute toxicity – oral endpoint
The study with the lowest LD50 was chosen. Key study (reliability: 1).

Justification for selection of acute toxicity – inhalation endpoint
Data waiving (other justification): In accordance with column 2 of REACH Annex VIII, the study does not need to be conducted since the substance is manufactured and commercialised as a water solution and the vapour pressure of the substance is low.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Acute oral toxicity:

Based on the available data, the LD50 is 300 -2000 mg active ingredient/kg bw. These findings support the classification as Acute Oral Toxicity - Category 4. The supporting study on the analogue also supports this classification.

Acute dermal toxicity:

Based on the available data, the LD50 is greater than 2000 mg/kg. Therefore, the substance is not classified.

 

Acute inhalation toxicity:

No data available. The study does not need to be conducted since the substance is manufactured and commercialised as a water solution and the vapour pressure of the substance is low.