Essential oil of Citrus sinensis (Rutaceae) peel, terpene-free

Vapour pressure

Link to relevant study record(s)

Reference

Endpoint:

vapour pressure

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

Study Initiation Date: 11 May 2020; Study Completion Date: 14 May 2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
iSafeRat® – in Silico Algorithms For Environmental Risk And Toxicity

2. MODEL (incl. version number)
iSafeRat® VP v1.3

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
linalool OC(C=C)(CCC=C(C)C)C
decanal O=CCCCCCCCCC
geranial O=CC=C(CCC=C(C)C)C
α-copaene C(CC(C1C(C2)C(C)C)C3(C2)C)=C(C)C31
α-terpineol OC(C(CCC(=C1)C)C1)(C)C
neral O=CC=C(CCC=C(C)C)C
valencene C(C(C(CC1)C)(CC(C(=C)C)C2)C)(=C1)C2
β-copaene C=C1C2C3(C(C2C(CC3)C(C)C)CC1)C
lauric aldehyde O=CCCCCCCCCCCC
citronellal O=CCC(CCC=C(C)C)C
δ-cadinene C(=C(CC1)C)C(C1=C(C2)C)C(C2)C(C)C
perillic aldehyde O=CC(=CCC1C(=C)C)CC1
caryophyllene C(=CCCC(C(C(C1(C)C)C2)C1)=C)(C2)C
β-cubebene C=C1C2C3(C2C(C(C)C)CCC3C)CC1
germacrene D CC1=CCCC(=C)C=CC(CC1)C(C)C
β-elemene C(C(C(C=C)(CCC1C(=C)C)C)C1)(=C)C
β-sinensal O=CC(=CCCC(=CCCC(C=C)=C)C)C
carvone O=C(C(=CCC1C(=C)C)C)C1
citronellol OCCC(CCC=C(C)C)C
decanol OCCCCCCCCCC

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

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 104 (Vapour Pressure Curve)

Deviations:

not applicable

Remarks:

QSAR model per constituent

Principles of method if other than guideline:

The VAPOUR PRESSURE of each mixture constituent was determined using the iSafeRat® VP model which predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 104. This model is based on a serie of linear relationships in which validated boiling point values are plotted against the log of vapour pressure values, where the pressure is in Pascals. Several regressions have been determined depending on the capability of the substance to participate in intermolecular interactions, such as hydrogen bonding. They form different local models.

GLP compliance:

no

Type of method:

other: QSAR model

Remarks:

In the majority of cases data for vapour pressure were obtained from the following methods described in the OECD Guideline No. 104: isoteniscope, dynamic, static, effusion (vapour pressure balance or loss of weight) and gas saturation methods.

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

23.5 Pa

Remarks on result:

other: linalool

Remarks:

95CI: [20.5;27.0] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

35.2 Pa

Remarks on result:

other: decanal

Remarks:

95CI: [31.1;39.7] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

17 Pa

Remarks on result:

other: geranial

Remarks:

95CI: [14.8;19.6] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

13.1 Pa

Remarks on result:

other: α-copaene

Remarks:

95CI: [11.5;14.9] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

7.58 Pa

Remarks on result:

other: α-terpineol

Remarks:

95CI: [6.43;8.94] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

27.9 Pa

Remarks on result:

other: neral

Remarks:

95CI: [24.5;31.7] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

10.7 Pa

Remarks on result:

other: valencene

Remarks:

95CI: [9.40;12.2] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

21 Pa

Remarks on result:

other: β-copaene

Remarks:

95CI: [18.7;23.5] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

4.4 Pa

Remarks on result:

other: lauric aldehyde

Remarks:

95CI: [3.7;5.23] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

47.4 Pa

Remarks on result:

other: citronellal

Remarks:

95CI: [42.2;53.2]

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

2.91 Pa

Remarks on result:

other: δ-cadinene

Remarks:

95CI: [2.49;3.41] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

10.7 Pa

Remarks on result:

other: perillic aldehyde

Remarks:

95CI: [9.17;12.4] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

9.7 Pa

Remarks on result:

other: caryophyllene

Remarks:

95CI: [8.50;11.1] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

21 Pa

Remarks on result:

other: β-cubebene

Remarks:

95CI: [18.7;23.5] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

7.35 Pa

Remarks on result:

other: germacrene D

Remarks:

95CI: [6.41;8.44] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

22.1 Pa

Remarks on result:

other: β-elemene

Remarks:

95CI: [0.814;1.25] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

1.01 Pa

Remarks on result:

other: β-sinensal

Remarks:

95CI: [0.814;1.25] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

16.3 Pa

Remarks on result:

other: carvone

Remarks:

95CI: [14.2;18.8] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

1.86 Pa

Remarks on result:

other: citronellol

Remarks:

95CI: [1.40;2.48] Pa

Key result

Test no.:

#1

Temp.:

25 °C

Vapour pressure:

1.42 Pa

Remarks on result:

other: decanol

Remarks:

95CI: [1.05;1.90] Pa

The iSafeRat® HA-QSAR predicts Vapour Pressure using the Boiling Point as an input.

Constituents	Boiling point (°C)	references
linalool	196.3	(ECHA, 2010)
decanal	212	(Haynes, 2014)
geranial	229	(Lide, 2005)
α-copaene	248.5	(Lide, 2009)
α-terpineol	219.5	(Lewis, 2012)
neral	217.44	(US EPA, 2010)
valencene	253.52	(US EPA, 2010)
β-copaene	236.77	(US EPA, 2010)
lauric aldehyde	260.8	(US EPA, 2000)
citronellal	205	(Haynes, 2014)
δ-cadinene	286	(EFSA, 2011a)
perillic aldehyde	240	(US EPA, 2000)
caryophyllene	256	(EFSA, 2011b)
β-cubebene	236.77	(US EPA, 2010)
germacrene D	262.9	(US EPA, 2010)
β-elemene	235.4	(US EPA, 2010)
β-sinensal	295.41	(US EPA, 2010)
carvone	230	(NTP, 1992)
citronellol	224	(Haynes, 2014)
decanol	229	(Haynes, 2014)

 

Descriptor domain

The descriptor domain has been reported for each constituent of the test item. The results are as follows:

Constituents	descriptor domain (BP in °C)	status
linalool	[82.3 ; 279.2]	inside domain
decanal	[30.7 ; 256]	inside domain
geranial	[30.7 ; 256]	inside domain
α-copaene	[26 ; 243.5]	not in domain
α-terpineol	[82.3 ; 279.2]	inside domain
neral	[30.7 ; 256]	inside domain
valencene	[26 ; 243.5]	not in domain
β-copaene	[26 ; 243.5]	inside domain
lauric aldehyde	[30.7 ; 256]	not in domain
citronellal	[30.7 ; 256]	inside domain
δ-cadinene	[26 ; 243.5]	not in domain
perillic aldehyde	[30.7 ; 256]	inside domain
caryophyllene	[26 ; 243.5]	not in domain
β-cubebene	[26 ; 243.5]	inside domain
germacrene D	[26 ; 243.5]	not in domain
β-elemene	[26 ; 243.5]	inside domain
β-sinensal	[30.7 ; 256]	not in domain
carvone	[30.7 ; 256]	inside domain
citronellol	[64.7 ; 282]	inside domain
decanol	[64.7 ; 282]	inside domain

13 constituents out of 20 fall inside descriptor domain, including the 8 constituents with the highest mass fractions. The remaining 7 constituents fall outside descriptor domain, but inside mechanistic domain, and therefore their prediction by extrapolation is considered reliable with restrictions within the confidence interval. As described in the relevant QMRF report, the applicability domain was based on k-Nearest Neighbours approach taking into account 5 closest training neighbours (k=5).

 

Structural fragment domain                                                                                                                                          

All chemical groups within the molecular structure of each constituent are taken into account by the model.

 

Mechanism domain

The model is based on different Simple Linear Regression equations (i.e. local models), selected on the basis of an initial classification about the capability of the substance to participate in intermolecular interactions, such as hydrogen bonding. iSafeRat® VP includes the following local models, ranked by increasing intermolecular attractive interactions:

• Vapour pressure local model for Non-Polar Organic compounds: for compounds which can only participate in weak Van der Waals attractive forces (e.g. alkanes, halides, alkenes, thiols… etc.).


• Vapour pressure local model for Oxygenated, Non-Hydroxylated compounds: for compounds which can participate in strong Van der Waals attractive forces (e.g. ethers, mono-esters, ketones, aldehydes, epoxides, lactones, carbonates, (meth)acrylates).


• Vapour pressure local model for Oxygenated, Hydroxylated compounds (Secondary and Tertiary Alcohols and phenols), which can participate in hydrogen bonds.


• Vapour pressure local model for Oxygenated, Hydroxylated compounds (Primary Alcohols), which can participate in hydrogen bonds.


• Vapour pressure local model for Carboxylic Acids, which can participate in hydrogen bonds.

The descriptor domain has been reported for each constituent of the test item. All the constituents fell inside the mechanism domain and could be predicted using one of these local models.

Conclusions:

This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004). The constituents of the test item fall within the applicability domain of the model and were therefore reliably predicted for the VAPOUR PRESSURE, except for 7 constituents which fall inside mechanistic domain but outside descriptor domain. For these constituents, the extrapolated prediction is considered reliable with restrictions within the confidence interval. Therefore, this endpoint values can be considered valid and fit for purpose.

Executive summary:

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the VAPOUR PRESSURE of the consituents of the test item. This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) and predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 104, "Vapour Pressure" (OECD, 2006). The criterion predicted was the vapour pressure at 25°C in Pascals.

 

The VAPOUR PRESSURE of each mixture constituent was determined using the iSafeRat® VP model which predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 104. This model is based on a serie of linear relationships in which validated boiling point values are plotted against the log of vapour pressure values, where the pressure is in Pascals. Several regressions have been determined depending on the capability of the substance to participate in intermolecular interactions, such as hydrogen bonding. They form different local models.

 

This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004). The constituents of the test item fall within the applicability domain of the model and were therefore reliably predicted for the VAPOUR PRESSURE, except for 7 constituents which fall inside mechanistic domain but outside descriptor domain. For these constituents, the extrapolated prediction is considered reliable with restrictions within the confidence interval. Therefore, this endpoint values can be considered valid and fit for purpose.

 

The VAPOUR PRESSURE of the constituents of the test item was determined as follow:

Constituents	vapour pressure (Pa) at 25 °C	95% confidence limits (Pa)	Applicability Domain
linalool	2,35E+01	2,05E+01 - 2.70E+01	inside domain
decanal	3,52E+01	3,11E+01 - 3.97E+01	inside domain
geranial	1,70E+01	1,48E+01 - 1.96E+01	inside domain
α-copaene	1,31E+01	1,15E+01 - 1.49E+01	extrapolated
α-terpineol	7,58E+00	6,43E+00 - 8.94E+00	inside domain
neral	2,79E+01	2,45E+01 - 3.17E+01	inside domain
valencene	1,07E+01	9,40E+00 - 1.22E+01	extrapolated
β-copaene	2,10E+01	1,87E+01 - 2.35E+01	inside domain
lauric aldehyde	4,40E+00	3,70E+00 - 5.23E+00	extrapolated
citronellal	4,74E+01	4,22E+01 - 5.32E+01	inside domain
δ-cadinene	2,91E+00	2,49E+00 - 3.41E+00	extrapolated
perillic aldehyde	1,07E+01	9,17E+00 - 1.24E+01	inside domain
caryophyllene	9,70E+00	8,50E+00 - 1.11E+01	extrapolated
β-cubebene	2,10E+01	1,87E+01 - 2.35E+01	inside domain
germacrene D	7,35E+00	6,41E+00 - 8.44E+00	extrapolated
β-elemene	2,21E+01	1,97E+01 - 2.48E+01	inside domain
β-sinensal	1,01E+00	8,14E-01 - 1.25E+00	extrapolated
carvone	1,63E+01	1,42E+01 - 1.88E+01	inside domain
citronellol	1,86E+00	1,40E+00 - 2.48E+00	inside domain
decanol	1,42E+00	1,05E+00 - 1.90E+00	inside domain

Description of key information

The vapour pressure of the major constituents of the substance at 25°C (20 constituents corresponding to more than 82% of the composition) are ranging between 1,01 and 47,4 Pa (estimated by QSAR).

Additional information

No study was conducted on the oil itself.

The test item is a natural complex substance (NCS). It is a mixture of several constituents, but 20 of them represent more than 82% of the mixture.

Vapour Pressure of these constituents was estimated using a Quantitative Structure-Property Relationship (QSPR) model, compliant with the OECD recommandations for QSAR modeling (OECD, 2004). This model is based on a serie of linear relationships in which validated boiling point values are plotted against the log of vapour pressure values, where the pressure is in Pascals. Several regressions have been determined depending on the capability of the substance to participate in intermolecular interactions, such as hydrogen bonding. They form different local models.

All the constituents of the test item fall within the applicability domain of the model and were reliably predicted for the Vapour Pressure, except for 7 constituents which fall inside mechanistic domain but outside descriptor domain. For these constituents, the extrapolated prediction is considered reliable with restrictions within the confidence interval. Therefore, this endpoint values can be considered valid and fit for purpose.

The Vapour Pressure of the constituents of the test item was determined as follow:

constituents	vapour pressure (Pa) at 25 °C	95% confidence intervals (Pa)
linalool	2,35E+01	2,05E+01 - 2.70E+01
decanal	3,52E+01	3,11E+01 - 3.97E+01
geranial	1,70E+01	1,48E+01 - 1.96E+01
α-copaene	1,31E+01	1,15E+01 - 1.49E+01
α-terpineol	7,58E+00	6,43E+00 - 8.94E+00
neral	2,79E+01	2,45E+01 - 3.17E+01
valencene	1,07E+01	9,40E+00 - 1.22E+01
β-copaene	2,10E+01	1,87E+01 - 2.35E+01
lauric aldehyde	4,40E+00	3,70E+00 - 5.23E+00
citronellal	4,74E+01	4,22E+01 - 5.32E+01
δ-cadinene	2,91E+00	2,49E+00 - 3.41E+00
perillic aldehyde	1,07E+01	9,17E+00 - 1.24E+01
caryophyllene	9,70E+00	8,50E+00 - 1.11E+01
β-cubebene	2,10E+01	1,87E+01 - 2.35E+01
germacrene D	7,35E+00	6,41E+00 - 8.44E+00
β-elemene	2,21E+01	1,97E+01 - 2.48E+01
β-sinensal	1,01E+00	8,14E-01 - 1.25E+00
carvone	1,63E+01	1,42E+01 - 1.88E+01
citronellol	1,86E+00	1,40E+00 - 2.48E+00
decanol	1,42E+00	1,05E+00 - 1.90E+00

No single key value was calculated (nor calculated weighted VP nor worst-case)