Oils, neroli

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Remarks:

Neroli Oil is a well-defined NCS (Natural Complex Substance), which is characterized to at least 90%. The water solubility of a NCS has a little meaning. According to the NCS protocol, a range of water solubility can be given from the calculated or measured values of the constituents of the NCS.

Justification for type of information:

1. SOFTWARE
Episuite platform (version 4.11)

2. MODEL (incl. version number)
WATERNT version 1.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
The CAS number database is used to input SMILES notations and chemical names onto the data entry by entering the Chemical Abstract Service (CAS) Registry number for each target substances (see annex I of the attached QPRF).

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QPRF

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

other: QSAR model

Title:

WATERNT v1.01a

Author:

U.S. Environmental Protection Agency

Year:

2010

Bibliographic source:

US EPA. [2008]. Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.00. United States Environmental Protection Agency, Washington, DC, USA

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSAR R.6

Deviations:

not applicable

Principles of method if other than guideline:

Meylan, W.M and P.H. Howard. 1995. Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 84:83-92.

Type of method:

other: calculation method (fragments)

Test material

Test material information

Constituent 1

Reference substance name:

(R)-p-mentha-1,8-diene

EC Number:

227-813-5

EC Name:

(R)-p-mentha-1,8-diene

Cas Number:

5989-27-5

Molecular formula:

C10H16

IUPAC Name:

4-isopropenyl-1-methylcyclohexene

Constituent 2

Reference substance name:

Linalool

EC Number:

201-134-4

EC Name:

Linalool

Cas Number:

78-70-6

Molecular formula:

C10H18O

IUPAC Name:

3,7-dimethylocta-1,6-dien-3-ol

Constituent 3

Reference substance name:

Pin-2(10)-ene

EC Number:

204-872-5

EC Name:

Pin-2(10)-ene

Cas Number:

127-91-3

Molecular formula:

C10H16

IUPAC Name:

6,6-dimethyl-2-methylenebicyclo[3.1.1]heptane

Constituent 4

Reference substance name:

Linalyl acetate

EC Number:

204-116-4

EC Name:

Linalyl acetate

Cas Number:

115-95-7

Molecular formula:

C12H20O2

IUPAC Name:

1,5-dimethyl-1-vinylhex-4-en-1-yl acetate

Constituent 5

Reference substance name:

3,7-dimethylocta-1,3,6-triene

EC Number:

237-641-2

EC Name:

3,7-dimethylocta-1,3,6-triene

Cas Number:

13877-91-3

Molecular formula:

C10H16

IUPAC Name:

3,7-dimethylocta-1,3,6-triene

Constituent 6

Reference substance name:

p-menth-1-en-8-ol

EC Number:

202-680-6

EC Name:

p-menth-1-en-8-ol

Cas Number:

98-55-5

Molecular formula:

C10H18O

IUPAC Name:

p-menth-1-en-8-ol

Constituent 7

Reference substance name:

7-methyl-3-methyleneocta-1,6-diene

EC Number:

204-622-5

EC Name:

7-methyl-3-methyleneocta-1,6-diene

Cas Number:

123-35-3

Molecular formula:

C10H16

IUPAC Name:

7-methyl-3-methyleneocta-1,6-diene

Constituent 8

Reference substance name:

Geranyl acetate

EC Number:

203-341-5

EC Name:

Geranyl acetate

Cas Number:

105-87-3

Molecular formula:

C12H20O2

IUPAC Name:

3,7-dimethylocta-2,6-dien-1-yl acetate

Constituent 9

Reference substance name:

Geraniol

EC Number:

203-377-1

EC Name:

Geraniol

Cas Number:

106-24-1

Molecular formula:

C10H18O

IUPAC Name:

3,7-dimethylocta-2,6-dien-1-ol

Constituent 10

Reference substance name:

3,7,11-trimethyldodeca-1,6,10-trien-3-ol,mixed isomers

EC Number:

230-597-5

EC Name:

3,7,11-trimethyldodeca-1,6,10-trien-3-ol,mixed isomers

Cas Number:

7212-44-4

Molecular formula:

C15H26O

IUPAC Name:

3,7,11-trimethyldodeca-1,6,10-trien-3-ol

Constituent 11

Reference substance name:

Nerol

EC Number:

203-378-7

EC Name:

Nerol

Cas Number:

106-25-2

Molecular formula:

C10H18O

IUPAC Name:

3,7-dimethylocta-2,6-dien-1-ol

Constituent 12

Reference substance name:

Farnesol

EC Number:

225-004-1

EC Name:

Farnesol

Cas Number:

4602-84-0

Molecular formula:

C15H26O

IUPAC Name:

3,7,11-trimethyldodeca-2,6,10-trien-1-ol

Constituent 13

Reference substance name:

Neryl acetate

EC Number:

205-459-2

EC Name:

Neryl acetate

Cas Number:

141-12-8

Molecular formula:

C12H20O2

IUPAC Name:

3,7-dimethylocta-2,6-dien-1-yl acetate

Constituent 14

Reference substance name:

Pin-2(3)-ene

EC Number:

201-291-9

EC Name:

Pin-2(3)-ene

Cas Number:

80-56-8

Molecular formula:

C10H16

IUPAC Name:

2,6,6-trimethylbicyclo[3.1.1]hept-2-ene

Constituent 15

Reference substance name:

Thuj-4(10)-ene

EC Number:

222-212-4

EC Name:

Thuj-4(10)-ene

Cas Number:

3387-41-5

Molecular formula:

C10H16

IUPAC Name:

1-isopropyl-4-methylenebicyclo[3.1.0]hexane

Constituent 16

Reference substance name:

Indole

EC Number:

204-420-7

EC Name:

Indole

Cas Number:

120-72-9

Molecular formula:

C8H7N

IUPAC Name:

1H-indole

Constituent 17

Reference substance name:

Methyl anthranilate

EC Number:

205-132-4

EC Name:

Methyl anthranilate

Cas Number:

134-20-3

Molecular formula:

C8H9NO2

IUPAC Name:

methyl 2-aminobenzoate

Test material form:

other: not applicable for in silico study

Results and discussion

Water solubility

Water solubility 1

Key result

Water solubility:

>= 2.012 - <= 3 560 mg/L

Temp.:

25 °C

Remarks on result:

other: Water solubility range for Neroli oil constituents

Water solubility 2

Key result

Water solubility:

13.8 mg/L

Temp.:

25 °C

Remarks on result:

other: d-limonene experimental water solubility from the training or the validation dataset of WATERNT

Water solubility 3

Key result

Water solubility:

1 590 mg/L

Temp.:

25 °C

Remarks on result:

other: Linalool experimental water solubility from the training or the validation dataset of WATERNT

Water solubility 4

Key result

Water solubility:

2.619 mg/L

Temp.:

25 °C

Remarks on result:

other: Beta-pinene QSAR predicted value

Water solubility 5

Key result

Water solubility:

40.617 mg/L

Temp.:

25 °C

Remarks on result:

other: Linalyl acetate QSAR predicted value

Water solubility 6

Key result

Water solubility:

2.012 mg/L

Temp.:

25 °C

Remarks on result:

other: Ocimene QSAR predicted value

Water solubility 7

Key result

Water solubility:

710 mg/L

Temp.:

25 °C

Remarks on result:

other: Terpineol experimental water solubility from the training or the validation dataset of WATERNT

Water solubility 8

Key result

Water solubility:

5.6 mg/L

Temp.:

25 °C

Remarks on result:

other: Myrcene experimental water solubility from the training or the validation dataset of WATERNT

Water solubility 9

Key result

Water solubility:

57.985 mg/L

Temp.:

25 °C

Remarks on result:

other: Geranyl acetate QSAR predicted value

Water solubility 10

Key result

Water solubility:

100 mg/L

Temp.:

25 °C

Remarks on result:

other: Geraniol experimental water solubility from the training or the validation dataset of WATERNT

Water solubility 11

Key result

Water solubility:

7.676 mg/L

Temp.:

25 °C

Remarks on result:

other: Nerolidol (trans) QSAR predicted value

Water solubility 12

Key result

Water solubility:

531 mg/L

Temp.:

25 °C

Remarks on result:

other: Nerol experimental water solubility from the training or the validation dataset of WATERNT

Water solubility 13

Key result

Water solubility:

10.958 mg/L

Temp.:

25 °C

Remarks on result:

other: Farnesol (trans trans) QSAR predicted value

Water solubility 14

Key result

Water solubility:

57.985 mg/L

Temp.:

25 °C

Remarks on result:

other: Neryl acetate QSAR predicted value

Water solubility 15

Key result

Water solubility:

2.49 mg/L

Temp.:

25 °C

Remarks on result:

other: Alpha-pinene experimental water solubility from the training or the validation dataset of WATERNT

Water solubility 16

Key result

Water solubility:

2.619 mg/L

Temp.:

25 °C

Remarks on result:

other: Sabinene QSAR predicted value

Water solubility 17

Key result

Water solubility:

3 560 mg/L

Temp.:

25 °C

Remarks on result:

other: Indole experimental water solubility from the training or the validation dataset of WATERNT

Water solubility 18

Key result

Water solubility:

2 850 mg/L

Temp.:

25 °C

Remarks on result:

other: Methyl anthranilate experimental water solubility from the training or the validation dataset of WATERNT

Any other information on results incl. tables

No study was conducted on the NCS itself.

The WATERNT model was used to predict the water solubility of the constituents of the test item.

Full details are provided in the QPRF attached.

All the constituents were within the applicability domain of the model and all the target substances were containing regular and common fragments included in this model; there are no limits to the mechanistic domain.

The water solubility was predicted as follows:

Target Substance	MW	WATERNT Estimated water solubility (mg/L) at 25°C	Experimental water solubility from the training or the validation dataset (mg/L) at 25°C
d-Limonene	136.24		13.8
Linalool	154.25		1590
β-pinene	136.24	2.6192
Linalyl acétate	196.29	40.617
Ocimene	136.24	2.012
α-terpineol	154.25		710
Myrcene	136.24		5.6
Geranyl acetate	196.29	57.985
Geraniol	154.25		100
Nerolidol (trans)	222.37	7.6761
Nerol	154.25		531
Farnesol (trans trans)	222.37	10.958
Neryl acetate	196.29	57.985
α-pinene	136.24		2.49
Sabinene	136.24	2.6192
Indole	117.15		3560
Methyl anthranilate	151.17		2850
The water solubility of the known constituents of the Substance were found to be in the range from 2.012 to 3560 mg/L at 25 °C.

Applicant's summary and conclusion

Conclusions:

The water solubility of the constituents of Neroli oil ranges between 2.012 and 3560 mg/L at 25 °C

Executive summary:

Neroli oil is a well-defined NCS containing multiple constituents.

As the water solubility for a NCS has little meaning, and according to the NCS protocol, the water solubility for the individual known consituents were predicted using the WATERNT v1.01 QSAR by US-EPA.

The water solubility of the constituents of Neroli Oil ranges between 2.012 and 3560 mg/L at 25 °C