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Description of key information

Key study: Read-across from experimental data on the analogue CAS No. 68155-09-9. Test according to OECD guideline 407 and EU guideline B.7. GLP study. The NOEL was considered to be 15 mg/kg/day (28-day oral toxicity study in rats).
Key study. Read-across from experimental data on the analogue Amides, C12-C18 (even numbered), N-[3-dimethylamino) propyl],N’-oxides. Test according to OECD guideline 408. GLP study. The NOAEL was considered to be 50 mg/kg/day (90-day oral toxicity study in rats).

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
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
Limit test:
no
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: Changes in the (fore)stomach, urinary bladder and red blood cell parameters at 500 mg/kg/day and the changes in the (fore)stomach at 150 mg/kg/day.
Critical effects observed:
not specified

The analogue Amides, C12-C18 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides 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.

 

Amides, C12-C18 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides where Alkyl chain=C8-C18,is a tertiary amine oxide where RCO- represents the fatty acids.The chemical contains the following carbon chain distribution:

C8

<10 %

C10

<10 %

C12

40-65 %

C14

10-26 %

C16

6-14 %

C18

2-24 %

 

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

a.- N-Oxide functionality

b.- Amide group

 

For the source substance, in the chemical structure, the RCO- is substituted by C8-C18 (predominantly C12 and C14, about 60-70% of the total) and for the target substance the RCO- is substituted by C12-C14.

 

Based on company experimental data (reported under the endpoint record Repeated dose toxicity: oral 90 days) on the analogue Amides, C12 -18 (even numbered), N-[3 -(dimethylamino) propyl], N'-oxides, the read-across approach is applied and the NOAEL for the substance Amides, C12-14 (even numbered), N-[3-(dimethylamino)propyl], N'-oxides is 50 mg/kg bw/day.

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

CAS Number

 

Source chemical

 

Target chemical

 

CHEMICAL NAME

 

Amides, C12-C18 (even numbered), 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.

 

Conclusions:
The "No Observed Effect Level" (NOAEL) was considered to be 50 mg/kg/day.
Executive summary:

The analogue Amides, C12-C18 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides 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.

 

Based on company experimental data (reported under the endpoint record Repeated dose toxicity: oral 90 days) on the analogue Amides, C12 -18 (even numbered), N-[3 -(dimethylamino) propyl], N'-oxides, the read-across approach is applied and the NOAEL for the substance Amides, C12-14 (even numbered), N-[3-(dimethylamino)propyl], N'-oxides is 50 mg/kg bw/day.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
The key study is of high quality with Klimisch score = 2, since read-across from a GLP compliant and Klimisch score = 1 study.

Additional information

Key study: Read-across from experimental data on the analogue Amides, C12-C18 (even numbered), N-[3 -dimethylamino) propyl],N’-oxides. Test according to OECD guideline 408 (Repeated dose 90 -Day oral toxicity in rodents). GLP study.

Based on company experimental data (reported under the endpoint record Repeated dose toxicity: oral 90 days) on the analogue Amides, C12 -18 (even numbered), N-[3 -(dimethylamino) propyl], N'-oxides, the read-across approach is applied and the NOAEL for the substance Amides, C12-14 (even numbered), N-[3-(dimethylamino)propyl], N'-oxides is 50 mg/kg bw/day.

The analogue Amides, C12-C18 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides 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.

 

Amides, C12-C18 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides where Alkyl chain=C8-C18,is a tertiary amine oxide where RCO- represents the fatty acids.The chemical contains the following carbon chain distribution:

C8

<10 %

C10

<10 %

C12

40-65 %

C14

10-26 %

C16

6-14 %

C18

2-24 %

 

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

a.- N-Oxide functionality

b.- Amide group

 

For the source substance, in the chemical structure, the RCO- is substituted by C8-C18 (predominantly C12 and C14, about 60-70% of the total) and for the target substance the RCO- is substituted by C12-C14.

Key study: Read-across from experimental data on the analogue CAS No. 68155-09-9. Test according to OECD guideline 407 and EU guideline B.7 (28 -day oral toxicity study in rats).

Based on company experimental data (reported under the endpoint record Repeated dose toxicity: oral_56) on the analogue CAS No. 68155-09-9, the read-across approach is applied and the NOEL for the substance Amides, C12-14 (even numbered), N-[3-(dimethylamino)propyl], N'-oxides is 15 mg/kg bw/day.

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 repeated dose toxicity via oral route - systemic effects endpoint:
The study with the longest duration (90 days) was chosen (key study).

Justification for classification or non-classification

Based on the available data on repeated dose toxicity study, the substance is not classified for STOT RE.