Essential oil of Petitgrain obtained from the leaves and twigs of Citrus aurantium (Rutaceae) by distillation

Toxicity to aquatic algae and cyanobacteria

Administrative data

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

Not relevant

Reliability:

2 (reliable with restrictions)

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

Justification for type of information:

Petitgrain oil - citrus aurantum is an UVCB substance. Regarding the different solubility of its constituents that make the testing difficult and a known fraction >90%, calculation from the ecotoxicity of the known constituent appears as an acceptable approach.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Principles of method if other than guideline:

This calculation method 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. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test", (1) referenced as Method C.3 of Commission Regulation No. 440/2008 (2) adapted for testing of a mixture using the WAF method.
The growth inhibition of algae was determined using a validated calculation method for the Mode of Action (MOA) in question (non-polar narcosis). been validated in an internal publication for MOA 1 (non-polar narcosis) and acute exposure (Bicherel and Thomas, 2014) (3). The algorithm is based on a QSAR model which has been validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004) (4). The QSAR model is based on validated data from a training set of 40 chemicals derived from 72-hour test on algae, for which the concentrations of the test item had been determined by chemical analyses over the test period. Further to this the effective loading rate of the WAF is determined by using a series of calculation steps using phase equilibrium thermodynamics and excluding the non-bioavailable fraction, this approach is based on validated data derived from 72-hour ErL50 tests on algae, for which the concentrations of the test item had been determined by chemical analyses over the test period.
(1) OECD Guideline for testing of chemicals No. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test", adopted March 23, 2006; Annex 5 corrected July 28, 2011.
(2) Commission Regulation (EC) No. 761/2009 amending Regulation (EC) No. 440/2008, Part C, C.3.: "Algal Inhibition Test", p. 36-56, Official Journal of the European Union (EN), dated August 24, 2009, L 220:1-94.
(3) Bicherel P and Thomas PC (2014) iSafeRat® WAF calculation method to predict acute aquatic toxicity. Position paper prepared by KREATiS.
(4) OECD (2004) Principles for the validation, for regulatory purposes, of (Quantitative) Structure Activity-Relationship Models, http://www.oecd.org/env/ehs/risk-assessment/oecdquantitativestructure-activityrelationshipsprojectqsars.htm

GLP compliance:

no

Remarks:

Not required for a calculation based on multiple QSARs method.

Test material

Test material information

Constituent 1

Reference substance name:

Essential oil of Petitgrain obtained from the leaves and twigs of Citrus aurantium (Rutaceae) by distillation

EC Number:

946-433-7

Cas Number:

Not available

Molecular formula:

Not applicable for a natural complex substance (UVCB)

IUPAC Name:

Essential oil of Petitgrain obtained from the leaves and twigs of Citrus aurantium (Rutaceae) by distillation

Test material form:

other: not applicable for in silico study

Details on test material:

- Name of test material (as cited in study report): Petitgrain oil
- Commercially available test material - not applicable for in silico study

Specific details on test material used for the study:

All the constituents with a concentration above 1% were taken into account to describe "typical" and "worst-case" compositions. The worst-case” composition was calculated by using the maximum concentration – instead of the typical concentration – for the more predicted ecotoxic constituents (ErC50≤1mg/l), and the concentrations of the other constituents corrected in order to achieve a 100% mixture. For the prediction, only the constituents which concentration is above 1% are taken into account.

constituents mass fraction (%) within typical composition mass fraction (%) within “worst-case” composition
linalyl acetate 48.00 38.40
linalool 25.00 20.00
geraniol 3.00 2.40
α-terpineol 5.50 4.40
geranyl acetate 4.40 3.20
limonene 1.00 4.00
myrcene 2.50 4.00
β-ocimene 3.50 2.80
nerol 1.00 0.80
neryl acetate 2.00 1.60
β-pinene 1.00 3.00
α-terpinyl acetate 1.00 3.00
β-caryophyllene 1.00 3.00
α-pinene - 3.00
sabinene - 3.00
terpinolene - 3.00
TOTAL 98.50 96.60

Sampling and analysis

Analytical monitoring:

no

Remarks:

Not relevant for a calculation based on multiple QSARs method

Details on sampling:

Not relevant.

Results and discussion

Effect concentrations

Effect concentrations 1

Key result

Duration:

72 h

Dose descriptor:

EL50

Remarks:

ErL50

Effect conc.:

9.7 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr. (dissolved fraction)

Remarks:

Worst-case composition

Basis for effect:

growth rate

Remarks on result:

other: Calculation based on QSARs.

Remarks:

The effective loading rate of the WAF is determined by using a series of calculation steps using phase equilibrium thermodynamics and excluding the non-bioavailable fraction.

Effect concentrations 2

Duration:

72 h

Dose descriptor:

EL50

Remarks:

ErL50 WAF

Effect conc.:

16 mg/L

Nominal / measured:

nominal

Conc. based on:

act. ingr. (dissolved fraction)

Remarks:

Typical composition

Basis for effect:

growth rate

Remarks on result:

other: Calculation based on QSARs.

Remarks:

The effective loading rate of the WAF is determined by using a series of calculation steps using phase equilibrium thermodynamics and excluding the non-bioavailable fraction.

Any other information on results incl. tables

"Adapted water solubility" (solubility of the constituent * molar fraction * UNIFAC-approach activity coefficient), lead to concentrations in WAF as follows:

constituents              for the typical composition              for the “worstcase” composition

linalyl acetate                     7.44                                                        3.73

linalool                              3.88                                                       1.94

geraniol                            0.47                                                        0.23

α-terpineol                        0.85                                                        0.43

geranyl acetate                  0.62                                                        0.31

limonene                           0.10                                                        0.35

myrcene                           0.15                                                        0.21

β-ocimene                        0.20                                                        0.14

nerol                                0.16                                                         0.078

neryl acetate                    0.31                                                          0.16

β-pinene                         0.16                                                           0.29

α-terpinyl acetate            0.16                                                           0.29

β-caryophyllene              0.0014                                                       0.0033

α-pinene                            -                                                              0.17

sabinene                            -                                                              0.29

terpinolene                        -                                                               0.29

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Remarks:

QSAR model validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004).

Conclusions:

For a typical composition, ErL50 (mg test item.L-1) = 16 mg/l
For a "worst-case" composition, ErL50 (mg test item.L-1) = 9.7 mg/l

Executive summary:

By using a "known constituents approach" based on non-polar-narcosis MOA-1 QSARs and WAF "adapted water solubilities”, the algae 72h-ErL50 for a “worst-case composition” is estimated 9.7 mg/l.