Registration Dossier

Physical & Chemical properties

Endpoint summary

Administrative data

Description of key information

Additional information

In accordance with Article 13 (1) of Regulation (EC) No. 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met. In particular, information shall be generated whenever possible by means other than vertebrate animal tests, through the use of alternative methods, for example, in vitro methods or qualitative or quantitative structure-activity relationship models or from information from structurally related substances (grouping or read-across).” According to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006, substances may be considered as a group provided that their physicochemical and toxicological characteristics are likely to be similar or follow a regular pattern as a result of structural similarity. The substances within the analogue approach are considered to apply to these general rules and the similarity is justified on basis of scope of variability and overlapping of composition, representative molecular structure, physico-chemical properties and toxicological profiles. There is convincing evidence that these chemicals lie in the overall common profile of this analogue approach. The key points that the target and the source substance share are:

Common functional groups:

The target substance and the source substanceare secondary amides which belong to the chemical class of N-Fatty Alkyl Amides of Saturated and Unsaturated Fatty Acids. Their structures consist of two linear carbon chains (i.e. not branched but potentially containing a C=C double bond) of chain length C14 to C24,and predominantly C16 and C18, linked by an amide moiety, -C(=O)NH-, and with the total number of carbon atoms generally falling within the range of > C32 and < C36.

Similar physico-chemical properties:

For the purpose of read-across of (eco)toxicity data, the most relevant physico-chemical parameters are physical state (appearance), vapour pressure, octanol/water partition coefficient and water solubility. Each of the substances is solid in form, and they have in common a low water solubility (<0.1 mg/L), high log Pow(> 5) and low vapour pressure (< 0 Pa at 25 °C).

Similar metabolic pathways:

The target and source substance are anticipated to be hydrolysed in the gastrointestinal tract and/or liver, resulting in the generation of primary fatty amines (stearylamine or oleylamine) as well as the corresponding long-chain saturated fatty acids (C16:0 and C18:0). Hydrolysis represents the first chemical step in the absorption, distribution, metabolism and excretion pathways assumed to be similar between the target substance and the source substance. Following hydrolysis of fatty acid amides, fatty acids are readily absorbed by the intestinal mucosa and distribute systemically in the organism. The resulting long-chain fatty acids palmitic acid (C16:0) and stearic acid (C18:0) are primarily degraded via mitochondrial β-oxidation and the breakdown products are finally metabolised for energy generation. The second hydrolysis product, the primary fatty amine (oleylamine or stearylamine), may be oxidatively deaminated by monoaminooxidases to yield the corresponding aldehyde and ammonia. The aldehyde may be further oxidised via the enzymatic action of aldehyde dehydrogenase to the corresponding carboxylic acid, which may be fed into further metabolic pathways such as beta-oxidation. Ammonia resulting from the oxidative deamination of the hydrolysis product stearylamine and oleylamine is likewise readily absorbed and distributed within the body, especially in liver, where it is detoxified via the urea cycle. The resulting urea is transported to the kidneys, where it will either be re-absorbed and fed into physiological pathways, or directly excreted via urine.

Common properties for environmental fate & eco-toxicological profile of the target and source substance:

Considering the low water solubility and the potential for adsorption to organic soil and sediment particles, the main compartment for environmental distribution is expected to be soil and sediment. Nevertheless, once this contact takes place, these substances are expected to be removed from the water column to a significant degree as the substance will be physically removed in sewage treatment plants due to the low water solubility and high adsorption potential to sewage sludge. Thus, discharged concentrations of these substance (if at all) into the aqueous/sediment and soil compartment are likely to be low. Evaporation into air and the transport through the atmospheric compartment is not expected since the target substance and the source substance are not volatile based on the low vapour pressure. Moreover, bioaccumulation is assumed to be low based on the insolubility of amides of saturated and unsaturated fatty acids. It is not likely that they can be found in the aquatic environment in high concentrations. Additionally, a bioaccumulation test is technically hardly feasible due to the high insolubility of the substances and is not necessary due to the non-hazardous character of the substances. Available data for the target and the source substance showed that the substances are of low toxicity to aquatic organisms as no effects were observed in acute studies up to the limit of water solubility (fish, aquatic invertebrates and algae). Target and source substance did not exhibit any effects on aquatic microorganisms. Therefore, effects on the microorganism community and the degradation process in sewage treatment plants are not anticipated.

Common levels and mode of human health related effects:

The available data indicate that the target and source substance have similar toxicokinetic behaviour (low bioavailability of the parent substance; anticipated hydrolysis of the amide bond followed by absorption, distribution, metabolism and excretion of the breakdown products) and that the constant pattern consists in a lack of potency change of properties. Thus, based on the available data, the target and the source substance of the analogue approach show a low acute oral toxicity and no potential for skin or eye irritation and no skin sensitisation properties. Furthermore, the target and source substance are not mutagenic in bacteria (for the source substance there is only data for bacteria available).

Physico-chemical properties

ID No.

Target

Source 1

CAS No.

16260-09-6

13276-08-9

Substance name

(Z)-N-Octadec-9-enylhexadecan-1-amide

N-Octadecylstearamide

Common name

Oleyl Palmitamide

Stearyl Stearamide

SMILES code

O=C(NCCCCCCCC\C=C/CCCCCCCC)CCCCCCCCCCCCCCC

O=C(NCCCCCCCCCCCCCCCCCC)CCCCCCCCCCCCCCCCC

Molecular weight [g/mol]

505.90

535.57

Physical state

Solid, Gardner 1.0

Solid, powder, Gardner max. 5.0

Melting Point [°C]

Experimental result:65°C

Experimental result: 85 - 95°C

Boiling Point [°C]

Experimental result:boiling and/or thermal decomposition atapproximately428 °C (1012 hPa)

Predicted result: 526.8 °C at 1013 hPa

(ChemSpider, 2013)

Relative density at 20 °C

Experimental result:(relative density): 0.94

Predicted result: 0.85 g/cm3

(ChemSpider, 2013)

Vapour pressure at 20 °C

Estimation result: 8.3E-05 Pa at 20 °C

Predicted result: 0 Pa 25°C

(ChemSpider, 2013)

Partition Coefficient    (log Pow)

Experimental result:Log Kow: > 5.7 at 23°C

Experimental result: 16.5(1)

(ChemSpider, 2013)

Water solubility at 20 °C [g/L]

Experimental result:< 0.01 mg/L at 20°C

n/a

Common origin

Manufacturing and associated similar structure characteristics

The target substance, (Z)-N-octadec-9-enylhexadecan-1-amide (oleyl palmitamide, CAS16260-09-6), and the source substance, N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9), are secondary N-alkyl alkylamides produced from a coupling reaction between an appropriate fatty acid and a fatty amine (March, 1992). It should be noted that the original raw materials used for manufacture of the fatty amines are also similar (or the same) fatty acids.

All the fatty acids used are derived from natural fats and oils, and are primarily of plant origin; commercial material is, therefore, a variable mixture with a general composition ordinarily lying in the range C14-C24. They are either fully saturated or with a single C=C double bond, predominantly have an even number of C atoms, and are without any significant levels of branching in the alkyl chain.

(Z)-N-octadec-9-enylhexadecan-1-amide is prepared from hexadecanoic acid [palmitic acid; CAS 57-10-3] and (Z)-octadec-9-en-1-amine (oleylamine, CAS 112-90-3) which is itself a derivative of (Z)-N-octadec-9-enoic acid (oleic acid, CAS 112-80-1). The source substance N-octadecylstearamide (stearyl stearamide, CAS 13276 -08 -9) is prepared from octadecanoic acid (stearic acid, CAS 57-11-4) and 1-amino-octadecane (stearylamine, CAS 124-30-1) which is also a derivative of octadecanoic acid (stearic acid, CAS 57-11-4).

The natural variability of the raw materials, the fatty acids, means that the final product, the fatty amide, has a composition that itself varies from batch to batch. Indeed, the variability in composition of the fatty acid means that some such substances are considered as multiconstituent or even UVCB substances. However, both the target substance being registered, (Z)-N-octadec-9-enylhexadecan-1-amide (oleyl palmitamide, CAS16260-09-6), and the source substance, N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9), contain >80% of each single C chain length (C18:1+C16:0 and C18:0+C18:0, respectively) and are considered as monoconstituent substances.

Structural similarity

The target substance (Z)-N-octadec-9-enylhexadecan-1-amide (oleyl palmitamide, CAS16260-09-6) and the source substance N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9) are secondary amides which belong to the chemical class of N-Fatty Alkyl Amides of Saturated and Unsaturated Fatty Acids. Their structures consist of two linear carbon chains (i.e. not branched but potentially containing a C=C double bond) of chain length C14 to C24, and predominantly C16 and C18, linked by an amide moiety, -C(=O)NH-, and with the total number of carbon atoms generally falling within the range > C28 and < C36. The substances are solids at ambient conditions. For details, see Analogue Justification in Section 13.

Physico-chemical properties

Physical state and melting point

The target and the source substances are solid at ambient temperature and pressure. The measured melting point of the target substance is 65°C. The measured melting point of the source substance N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9) is 85 - 95°C.

Boiling point

The target substance shows a boiling and/or thermal decomposition with evaporation of the decomposition products from 428°C. The predicted boiling point of the source substance N- octadecylstearamide (stearyl stearamide, CAS 13276-08-9) is 526.8°C (ChemSpider, 2013).

Density

The measured relative density of the target substance is 0.94 at 20°C. The predicted density of the source substance N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9) is 0.85 g/cm³ (ChemSpider, 2013).

Vapour pressure

The measured vapour pressure of the target substance is 8.3E-05 Pa at 20°C. The predicted vapour pressure of the source substance N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9) is 0 Pa at 25°C (ChemSpider, 2013).

The predicted value of 0 Pa for the source substance is imprecise. However, this may be taken to be indicative that the source substance, like the target substance, has an extremely low vapour pressure.

Octanol-water partition coefficient (log Pow)

The measured log Kow value of the target substance is > 5.7 at 23°C. The measured log Kow value of the source substance N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9) is 16.5 (ChemSpider, 2013).

Water solubility

The measured water solubility value of the target substance is < 0.01 mg/L at 20°C. No measured value is available for the source substance N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9), but based on the chemical structure water solubility is expected to be comparable or even lower.

Surface tension

The surface tension measurement of the target substance does not need to be conducted as the water solubility is below 1 mg/L at 20 °C.

The water solubility of the source substance N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9) is also expected to be below 1 mg/L at 20°C; therefore, surface tension is also not available for that substance.

Flammability

The target substance is non-flammable; pyrophoricity and flammability on contact with water are not expected. The source substance N-octadecylstearamide (stearyl stearamide, CAS 13276-08-9) is also predicted to be non-flammable, and pyrophoricity and flammability on contact with water are not expected.