Ethyl decanoate

Endpoint summary

Description of key information

Based on the available study performed on the source substance isopropyl myristate, and on the category approach, the category substances are considered to be not sensitising to skin. Additionally, QSAR and prediction were performed and showed no sensitisation concerning ethyl decanoate which is consistent with the category approach. Taking together, all the available information showed that the target substance, ethyl decanoate is considered as not inducing skin sensitisation according to CLP criteria.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

See "Assessment reports" section 13 or "Categories" section for the justification and rationale document for category approach.

Key result

Remarks on result:

no indication of skin sensitisation

Table 1: Results from available key studies on the source substances of the category

Common name	CAS	Fatty acid chain length	Type of  alcohol	MW	Appareance	Skin sensitisation
Ethyl decanoate	110-38-3	C10	ethanol	200.32	Liquid	No data
Ethylundecylenate	692-86-4	C11	ethanol	212.33	liquid	No data
Isopropyllaurate	10233-13-3	C12	Isopropanol	242,41	Liquid	no data
Octyloctanoate	2306-88-9	C8	octanol(C8)	256,42	Liquid	no data
Isopropyl myristate	110-27-0	C14	Isopropanol	270,46	Liquid	Experimental result: Not sensitising
Dodecanoic hexylester	34316-64-8	C12	Hexanol(C6)	284,49	Liquid	no data
Ethyl linoleate	544-35-4	C18:2	ethanol	308,5	Liquid	no data
Ethyl oleate	111-62-6	C18:1	ethanol	310.52	Liquid	no data
2-ethylhexyl laurate	20292-08-4	C12	2-Ethyl-Hexanol	312,53	Liquid	no data
Fatty acids, coco, 2-ethylhexyl esters	92044-87-6	C12-14	2-ethylhexanol	312.53 – 340.60	liquid	No data

 

The physico-chemical properties of the category members are similar or follow a regular pattern over the category. The patterns observed depend on the fatty acid and alcohol chain length. Molecular weight of the category members ranges from 200.32 g/mol (ethyl decanoate, target substance) to 340.6 g/mol (fatty acids, coco, 2-ethylhexyl esters). The physical appearance is related to the chain length of the fatty acid and the saturation or unsaturation. These substances are all liquids.

Based on the available study, th isopropyl myristate was not sensitizing. This result is in consistent with skin irritation studies performed, and the expected low toxicity of the category substances.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the available study, isopropyl myristate was not sensitizing. This result is in consistent with skin irritation studies performed, and the expected low toxicity of the category substances.

Executive summary:

According to the Regulation (EC) NO. 1907/2006, Annex XI, 1.5, A read-across category for short chain fatty acid was performed in order to provide informations on ethyl decanoate CAS 110-38-3.

This category was based on common and shared physico-chemical and structural properties as:

-       common functional group,

-       common precursors and the likehood of common impurities as well as common breakdown products via biological processes, which are chemically structurally similar, and

-       constant pattern in the changing of the potency of the properties across the category.

The category substances are fatty acid esters covering chain length C8 to C18 satured or unsatured linked to alcohol including ethanol, isopropanol, octanol, hexanol and 2-ethylhexanol. These substances showed similar physico-chemical properties as very low solubility in water, not volatile, ready biodegradable and high log Kow. The substances are expected to have same toxicity behavior according to the common structural and physico-chemical similarities. Indeed, they are expected to be hydrolyzed in same way when applied dermally.

As expected, none of the sensitisation tests performed showed adverse effect. Hence, the category substances are not classified for acute dermal hazard according to CLP criteria.

Reference 2

Endpoint:

skin sensitisation: in chemico

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

6 April 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

See attached-document QPRF in section "Attached justification".

Qualifier:

no guideline required

Principles of method if other than guideline:

(Q)SAR prediction was performed using OECD ToolBox v4.1.

GLP compliance:

no

Details on the study design:

The study was performed using OECD ToolBox (v4.1). This prediction was performed in order to provide information on potential sensitizing effect on decanoic acid. The prediction is based on structural analogues (nonanoic acid, enanthic acid, palmitylglycine, oleic acid) with relevant data for read across. The predicted endpoint is skin sensitisation from experimental data coming from well identifiable test systems: OECD 406 (Buehler Test, Guinea Pig Maximisation Test). The present prediction was done in the frame of the EU regulations dealing with chemical substances, such as REACh, Biocide, CLP.

Key result

Remarks on result:

no indication of skin sensitisation

Other effects / acceptance of results:

The prediction is based on 5 values, 5 of them (100%) equal to predicted value. Prediction confidence is measured by the p-value: 0.0313.

Table 1: Data matrix for the target and the analogue substances

 

Structure
CAS number	334-48-5	112-05-0	111-14-8	2441-41-0	112-80-1
Chemical name	Decanoicacid	Nonanoicacid	enanthicacid	Palmitylglycine	Oleic acid
Smiles Code	CCCCCCCCCC(O)=O	CCCCCCCCC(O)=O	CCCCCCC(O)=O	CCCCCCCCCCCCCCCC(=O)NCC(O)=O	CCCCCCCCC=CCCCCCCCC(O)=O
Profiles used forgrouping/subcategorization
Organic functional groups (primary grouping)	Carboxylic acid; Surfactants - Anionic	Carboxylic acid; Surfactants - Anionic	Carboxylic acid; Surfactants - Anionic	Carboxylic acid; Organic amide andthioamide; Surfactants - Anionic	Alkene; Allyl; Carboxylic acid; Surfactants - Anionic
Organic functional groups (nested) (subcategorization)	Surfactants - Anionic	Surfactants - Anionic	Surfactants - Anionic	Surfactants - Anionic	Surfactants - Anionic
			General Mechanistic
Protein binding by OASIS	No alert found	No alert found	No alert found	No alert found	No alert found
Protein binding by OECD	No alert found	No alert found	No alert found	No alert found	No alert found
Protein binding potency	Not possible to classify according to these rules (GSH)	Not possible to classify according to these rules (GSH)	Not possible to classify according to these rules (GSH)	Not possible to classify according to these rules (GSH)	Not possible to classify according to these rules (GSH)
Protein binding potencyCys(DPRA 13%)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non- Conjugated carboxylic acids and esters (non reactive)
Protein binding potency Lys (DPRA 13%)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Anionic surfactants; DPRA less than 9% (DPRA 13%) >> Non- Conjugated carboxylic acids and esters (non reactive)
			Endpoint Specific
Protein binding alerts for skin sensitization according to GHS	No alert found	No alert found	No alert found	No alert found	No alert found
Protein binding alerts for skin sensitization by OASIS	No alert found	No alert found	No alert found	No alert found	No alert found
Protein Binding Potency h-CLAT	No alert found	No alert found	No alert found	No alert found	No alert found

 

Further details on results were given in attached-document QPRF in section "attached-justification".

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the prediction performed using OECD ToolBox (v4.1) for skin sensitisation endpoint, decanoic acid should be considered as not inducing skin sensitisation according to CLP criteria.

Reference 3

Endpoint:

skin sensitisation: in chemico

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

18 March 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Qualifier:

no guideline required

Principles of method if other than guideline:

(Q)SAR AOP prediction was performed using OECD ToolBox v4.1.

GLP compliance:

no

Details on the study design:

The present AOP evaluation was done in the frame of the EU regulations dealing with chemical substances, such as REACh, Biocide, CLP…
This AOP relies on the analysis of the available mechanistic knowledge (sequence of events) of the sensitization response initiated by covalent binding to proteins.
The workflow implemented in the OECD Toolbox v4.1 helps to consider the pathways likely to elicit a skin sensitisation potential:
- Chemical structure and properties,
- Molecular initiating events,
- Cellular response
- Organ response
- Organism response.

The different step in the AOP are :
- Molecular Initiating event (MIE) : Protein binding alerts
- Key Event 1 : Molecular interactions
- Key Event 2 : Cellular responses (gene expression)
- Key Event 3: Cellular responses (activation of dendritic cells)
- Key Event 4: Organ reponses (T-cell activation)
- Adverse outcome : in vivo organism response (GPMT)

Source and informations for each key event are experimental data, read-across or profiling with metaboçlism simulation (from the OECD Toolbox).

For each Molecular initiating event, key event and adverse outcome, results of the assessment are detailed in the attached-report in "attached-justification" section.

Key result

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the AOP prediction performed using OECD ToolBox (v4.1), ethyl caprate should be considered as not inducing skin sensitisation according to CLP criteria.

Reference 4

Endpoint:

skin sensitisation: in chemico

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

6 April 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Qualifier:

no guideline required

Principles of method if other than guideline:

(Q)SAR prediction was performed using OECD ToolBox v4.1.

GLP compliance:

no

Details on the study design:

The study was performed using OECD ToolBox (v4.1). This prediction was performed in order to provide information on potential sensitizing effect on ethyl caprate (CAS 110-38-3). The prediction is based on structural analogues (methyl laurate, triethyl aconitate, butylacetate, substance CAS 58430-94-7, substance CAS 0-07-6) with relevant data for read across. The predicted endpoint is skin sensitisation from experimental data coming from well identifiable test systems: OECD 406 (Buehler Test, Guinea Pig Maximisation Test). The present prediction was done in the frame of the EU regulations dealing with chemical substances, such as REACh, Biocide, CLP.

Key result

Remarks on result:

no indication of skin sensitisation

Other effects / acceptance of results:

The prediction is based on 5 values, 4 of them (80.0%) equal to predicted value
Prediction confidence is measured by the p-value: 0.188

Table 1: Data matrix for the target and the analogue substances

 

Structure
CAS number	110-38-3	111-82-0	58430-94-7	Invalid CAS number: 0-03-0	123-86-4	Invalid CAS number: 0-07-6
Chemical name	Ethyldecanoate	methyl laurate	-	Triethyl_Aconitate	Butylacetate	-
Smiles Code	CCCCCCCCCC(=O)OCC	CCCCCCCCCCCC(=O)OC	CC(CCOC(C)=O)CC(C)(C)C	CCOC(=O)CC(=CC(=O)OCC)C(= O)OCC	CCCCOC(C)=O	CCCCCCCCCCCCCCCCCCC(= O)OC
Profiles used for grouping/subcategorization
Organic functional groups, NorbertHaider (checkmol) (primary grouping)	Carboxylic acid derivative; Carboxylic acid ester	Carboxylic acid derivative; Carboxylic acid ester	Carboxylic acid derivative; Carboxylic acid ester	Carboxylic acid derivative; Carboxylic acid ester	Carboxylic acid derivative; Carboxylic acid ester	Carboxylic acid derivative; Carboxylic acid ester
Protein binding alerts for skin sensitization according to GHS (subcategorization)	No alert found	No alert found	No alert found	No alert found	No alert found	No alert found
Protein binding potencyCys(DPRA 13%) (subcategorization)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)
			General Mechanistic
Protein binding by OASIS	No alert found	No alert found	No alert found	Michael addition >> Michael addition on conjugated systems with electron withdrawing group >>alpha,beta-Carbonyl compounds with polarized double bonds	No alert found	No alert found
Protein binding by OECD	No alert found	No alert found	No alert found	Michael addition >>Polarised Alkenes >>Polarisedalkene - esters	No alert found	No alert found
Protein binding potencyCys(DPRA 13%)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)
Protein binding potency Lys (DPRA 13%)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)	DPRA less than 9% (DPRA 13%) >> Non-Conjugated carboxylic acids and esters (non reactive)
Protein binding potency	Not possible to classify according to these rules (GSH)	Not possible to classify according to these rules (GSH)	Not possible to classify according to these rules (GSH)	Moderately reactive (GSH) >> Alkyl 2-alkenoates (MA)	Not possible to classify according to these rules (GSH)	Not possible to classify according to these rules (GSH)
			Endpoint Specific
Protein binding alerts for skin sensitization according to GHS	No alert found	No alert found	No alert found	No alert found	No alert found	No alert found
Protein binding alerts for skin sensitization by OASIS	No alert found	No alert found	No alert found	Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >>alpha,beta-Carbonyl compounds with polarized double bonds	No alert found	No alert found
Protein Binding Potency h-CLAT	No alert found	No alert found	No alert found	alpha, beta-Unsaturated esters	No alert found	No alert found

 

Other details on prediction performed was provided in attached-document QPRF in section "attached-justification".

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the prediction performed using OECD ToolBox (v4.1) for skin sensitisation endpoint, ethyl caprate should be considered as not inducing skin sensitisation according to CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

This category groups covers esters (including ethanol, isopropanol, octanol, hexanol and 2-ethylhexanol) linked to fatty acids chain satured and unsatured (C8 to C18). This category includes monoconstituent substances and UVCB substances varying fatty acid chain length and based on the alcohol sources. This category group was made in order to provide sufficient information for physico-chemical, environmental, ecotoxicological and toxicological caracterisation of ethyl decanoate (CAS 110-38-3). This approach covers these endpoints including skin irritation, eye irritation, and in vitro gene mutation study in bacteria for which some data on the target substance of the category are available.

This category includes:

-       Target substance:

o       Ethyl decanoate (CAS 110-38-3)

-       Source substances:

o       Ethyl undecylenate (CAS 692-86-4)

o       Isopropyl laurate (CAS 10233-13-3)

o       Octyl octanoate (CAS 2306-88-9)

o       Isopropyl myristate (CAS 110-27-0)

o       Dodecanoic hexyl ester (CAS 34316-64-8)

o       Ethyl linoleate (CAS 544-35-4)

o       Ethyl oleate (CAS 111-62-6)

o       2-Ethylhexyl laurate (CAS 20292-08-4)

o       Fatty acids, coco, 2-ethylhexyl esters (CAS 92044-87-6)

Summary of the available studies for skin sensitization assessment.

Isopropyl myristate CAS 110 -27 -0

A key study was available for skin sensitization assessment on the Isopropyl myristate. This study was performed with a Magnusson & Kligman method (guinea pigs maximisation test) similar to OECD Guideline 406. Pirbright Hartley guinea pigs were used. Intradermal and epicutaneaous induction phase was performed with Carboxymethylcellulose as vehicle with 5% concentration of test item for dermal application. The challenge phase was performed under occlusive condition and dermelly, the test item was used at 25% concentration. No sensitization was observed after challenge. Hence the test item Isopropyl myristate was not classified according to CLP criteria for skin sensitization.

Ethyl decanoate CAS 110-38-3

Two available studies were performed using OECD ToolBox (v4.1) on ethyl decanoate (target substance). Prediction and AOP were perfomed according to CLP regulations. None of the two predictions showed skin sensibilisation. Additionally, a prediction was performed on the decanoic acid. According to current litterature, ethyl decanoate could be hydrolized by skin lipase into decanoic acid and ethanol. Decanoic acid could vehicle potential sensitizing effect. Using OECD Toolbox v4.A, the predction showed no skin sensitising effect for decanoic acid.

Using a weight of evidence approach, informations from the read across category, predictions on ethyl decanoate (including the AOP prediction),on decanoic acid, did not showed skin sensitising properties for ethyl decanoate. Taking together, it can be stated that ethyl decanoate is not a skin sensitiser according to CLP criteria.

Justification for classification or non-classification

Based on the available study performed on the source substance isopropyl myristate, and on the category approach, the category substances are considered to be not sensitising to skin. Additionally, QSAR and prediction were performed and showed no sensitisation concerning ethyl decanoate which is consistent with the category approach. Taking together, all the available information showed that the target substance, ethyl decanoate is considered as not inducing skin sensitising substance according to CLP criteria.