Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
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)
Limit test:
no
Dose descriptor:
NOEL
Effect level:
100 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Reproductive 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 Toxicity to reproduction.001) on the analogue, the read-across approach is applied and the NOEL for reproductive and systemic toxicity for the substance Amides, C12-14 (even numbered), N-[3-(dimethylamino)propyl], N'-oxides is considered to be 100 mg/kg/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 oral administration of the substance to rats for a period of up to fifty-four consecutive days at dose levels of up to 100 mg/kg/day, did not result in any treatment-related effects. The ‘No Observed Effect Level’ (NOEL) for systemic toxicity was therefore considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity). The ‘No Observed Effect Level’ (NOEL) for reproductive toxicity was considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity).
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 Toxicity to reproduction.001) on the analogue, the read-across approach is applied and the NOEL for reproductive and systemic toxicity for the substance Amides, C12-14 (even numbered), N-[3-(dimethylamino)propyl], N'-oxides is considered to be 100 mg/kg/day.

 

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
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. Reproduction/Developmental toxicity screening test according to OECD guideline 421. GLP study.

The oral administration of the test material to rats for a period of up to fifty-four consecutive days at dose levels of up to 100 mg/kg/day, did not result in any treatment-related effects. The ‘No Observed Effect Level’ (NOEL) for systemic toxicity was therefore considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity). The ‘No Observed Effect Level’ (NOEL) for reproductive toxicity was considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity).

Data waiving: Two-generation reproductive toxicity study: The study does not need to be conducted since based on the available data from the reproduction/developmental toxicity screening test and the 28-day toxicity study, the test material did not cause any adverse effect on reproductive organs and tissues.

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.


Short description of key information:
Key study: Read-across from experimental data on the analogue Amides, C12-C18 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides. Reproduction/Developmental toxicity screening test according to OECD guideline 421. GLP study.

The ‘No Observed Effect Level’ (NOEL) for systemic toxicity was therefore considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity). The ‘No Observed Effect Level’ (NOEL) for reproductive toxicity was considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity).

Justification for selection of Effect on fertility via oral route:
Only one study available.

Effects on developmental toxicity

Description of key information
Key study: Read-across from experimental data on the analogue Amides, C12-C18 (even numbered), N-[3-(dimethylamino) propyl], N´-oxides. Reproduction/Developmental toxicity screening test according to OECD guideline 421. GLP study.  
The ‘No Observed Effect Level’ (NOEL) for systemic toxicity was therefore considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity). The ‘No Observed Effect Level’ (NOEL) for reproductive toxicity was considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
100 mg/kg bw/day
Study duration:
subacute
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. Reproduction/Developmental toxicity screening test according to OECD guideline 421. GLP study.

The oral administration of the test material to rats for a period of up to fifty-four consecutive days at dose levels of up to 100 mg/kg/day, did not result in any treatment-related effects. The ‘No Observed Effect Level’ (NOEL) for systemic toxicity was therefore considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity). The ‘No Observed Effect Level’ (NOEL) for reproductive toxicity was considered to be 100 mg/kg/day (incorporating a correction factor for 31.8% purity).

Data waiving: Pre-natal developmental toxicity study: The study does not need to be conducted since based on the available data from the reproduction/developmental toxicity screening test, the test material did not cause any adverse effects.

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.


Justification for selection of Effect on developmental toxicity: via oral route:
Only one study available (see Toxicity to reproduction.0.001 read-across endpoint record).
OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Justification for classification or non-classification

Based on the available data, the substance is not classified.

Additional information