Reaction mass of 6-ethyl-3-methyloct-5-en-1-ol and 6-ethyl-3-methyloct-6-en-1-ol

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The QSAR result is considered reliable according to OECD principles. The QSAR model is scientifically valid and Super Muguet falls within its applicability domain. A relaibility score of 2 has been assigned, which is the maximum for QSAR predictions.

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Methodology document for the ECOlogical Structure-Activity Relationship model (ECOSAR) Class Program. Windows version 1.11

Author:

Mayo-Bean KE, Moran KE, Meylan B & Ranslow P

Year:

2012

Bibliographic source:

http://www.epa.gov/oppt/newchems/tools/ecosartechfinal.pdf

Report date:

2012

Reference 2

Reference Type:

other: ECHA Guidance Document

Title:

ECHA Practical Guide 5: How to Report (Q)SARs

Author:

European Chemicals Agency

Year:

2012

Bibliographic source:

http://echa.europa.eu/documents/10162/13655/pg_report_qsars_en.pdf

Reference 3

Reference Type:

other: Software help file

Title:

ECOSAR v1.11 - Help file

Author:

US Environmental Protection Agency (EPA)

Year:

2012

Bibliographic source:

http://www.epa.gov/oppt/newchems/tools/ecosartechfinal.pdf

Materials and methods

Test guideline

Guideline:

other: REACH Guidance on QSARs R.6, May 2008

Principles of method if other than guideline:

ECOSAR v.1.11
Neutral Organics, 48-hr Daphnid LC50 QSAR

GLP compliance:

not specified

Remarks:

Not applicable: QSAR

Test material

Test material information

Constituent 1

Reference substance name:

(Z)-6-ethyl-3-methyloct-6-en-1-ol (Constituent 1)

IUPAC Name:

(Z)-6-ethyl-3-methyloct-6-en-1-ol (Constituent 1)

Constituent 2

Reference substance name:

(E)-6-ethyl-3-methyloct-6-en-1-ol (Constituent 2)

IUPAC Name:

(E)-6-ethyl-3-methyloct-6-en-1-ol (Constituent 2)

Constituent 3

Reference substance name:

6-ethyl-3-methyloct-5-en-1-ol (Constituent 3)

IUPAC Name:

6-ethyl-3-methyloct-5-en-1-ol (Constituent 3)

Details on test material:

SMILES:
OCCC(C)CCC(CC)=CC for Constituent 1 and 2
The prediction of the daphnia 48-hr LC50 using ECOSAR v1.11 is based on 2D structure and as such the result will be identical for the (Z) and (E)-isomers of 6-ethyl-3-methyloct-6-en-1-ol. Hence only one SMILES input was used to represent constituents 1 and 2.

CC/C(CC)=C/CC(C)CCO for Constituent 3

Log Kow :
4.046 (estimated value for all constituents, EPISuite Kowwin v1.68)
3.6 (measured value for all constituents; the partition coefficient n-octanol/water of Super Muguet was determined by the reverse HPLC method according to OECD guideline 117. The chromatogram shows two unresolved peaks, corresponding to partition coefficients (log value) of 3.6 for both peaks, indicating that all three stereoisomers have approximately the same log Kow)

The SMILES and log Kow are used in the ECOSAR v1.11 model.

Results and discussion

Effect concentrations

Effect concentrations 1

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

1.394 mg/L

Remarks on result:

other: Constituents 1 and 2 using estimated log Kow of 4.046

Effect concentrations 2

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

1.394 mg/L

Remarks on result:

other: Constituent 3 using estimated log Kow of 4.046

Effect concentrations 3

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

3.367 mg/L

Remarks on result:

other: Constituents 1 and 2 using measured log Kow of 3.6

Effect concentrations 4

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

3.367 mg/L

Remarks on result:

other: Constituent 3 using measured log Kow of 3.6

Details on results:

VALIDITY OF MODEL:
The ECOSAR Class Program and underlying methodology have been developed over a period of more than 25 years by EPA/OPPT. The current ECOSAR version (v1.11, May 2012) is programmed to identify 111 chemical classes and allows access to 704 QSARs for numerous endpoints and organisms. The neutral organic 48-hr Daphnid LC50 QSAR is one of these QSARs. The model is valid according to the following five OECD principles.

1. Defined Endpoint: Acute toxicity to invertebrates (Daphnid)
2. Unambiguous algorithm: Log 48-h LC50 = -0.858 (log Kow) + 1.3848
- to convert the LC50 from mmol/L to mg/L, multiply by the molecular weight of the substance)
- In ECOSAR version 1.11, all QSARs have been derived using pre-dicted log Kow values for the training set chemicals. The log Kow values were predicted using the KOWWIN program.
3. Applicability domain: The Neutral Organic SAR is applicable to non-ionizable and non-reactive chemicals with a Log Kow of < 5 and a molecular weight of < 1000.
4. Statistical characteristics: a) internal performance; n = 98, r2 = 0.7704, b) External validation; A number of supporting validation exercises have been performed in conjunction with EPA and other stakeholders on the ECOSAR models and are listed in the "Methodology Document for the Ecological Structure-Activity Relationship Model (ECOSAR) Class Program v1.11"
5. Mechanistic interpretation: The mechanistic basis for the model is nonpolar narcosis, which has been shown to be positively correlated with lipophilicity (as modelled by log Kow) up to a log Kow limit of 5 (for acute effects on fish and daphnia) and 6.4 (for green algae).

More detailed information is provided in the attached QMRF file.

PREDICTED VALUE (MODEL RESULT):
- SUPER MUGUET was predicted to have a daphid 48-hr LC50 of 1.394-3.367 mg/L.
- The ECOSAR v1.11 results files are attached for:
6-ethyl-3-methyloct-6-en-1-ol (constituent 1 and 2) using estimated log Kow
6-ethyl-3-methyloct-6-en-1-ol (constituent 1 and 2) using measured log Kow
6-ethyl-3-methyloct-5-en-1-ol (constituent 3) using estimated log Kow
6-ethyl-3-methyloct-5-en-1-ol (constituent 3) using measured log Kow

ADEQUACY PREDICTION:
- Super Muget is a non-ionised chemical. All three constituents have an estimated logKow of 4.046, measured log Kow of 3.6 and molecular weight of 167.1. As such it falls within the applicability domain described above.
- Super Muguet is a mixture of isomers. The stereochemical features will not affect the reliability of the prediction, which is based on 2D chemical structure and the predicted logarithm of the n-octanol / water partition coefficient. A separate prediction was performed for SMILES OCCC(C)CCC(CC)=CC (representing constituents 1 and 2) and for SMILES CC/C(CC)=C/CC(C)CCO (representing constituent 3). Both gave the same results. This is explained by the fact that 6-ethyl-3-methyloct-6-en-1-ol (constituent 1 and 2) and 6-ethyl-3-methyloct-5-en-1-ol (constituent 3) are assigned to the Neutral Organics ECOSAR and have the same log Kow.
- Based on the chemical structure, The ECOSAR programme attributes 6-ethyl-3-methyloct-6-en-1-ol (constituent 1 and 2) and 6-ethyl-3-methyloct-5-en-1-ol (constituent 3) to the chemical class of Neutral Organics. Experimentally derived high quality fish and green algae L(E)C50 values exist for Super Muguet. A comparison of these measured values with predicted L(E)C50 values derived from the ECOSAR Neutral Organic SAR confirms that Super Muguet acts via simple nonpolar narcosis (see table 1 in section "Any other information on results incl. tables").
- The prediction value can be considered reliable taking into account that i) predicted and experimental data for a close structural analogue are in close agreement (see QPRF for details and table 2 in section "Any other information on results incl. tables", and ii) predicted and experimental fish and Green Alage data for SUPER MUGUET using similar ECOSAR Neutral Organic SAR regressions are in close agreement (table 1).
- Moreover, the experimental and predicted values for SUPER MUGUET fall within the same acute aquatic hazard classification criterion range: E(L)C50 > 1mg/L and <= 10mg/L. Thus the daphnia 48-hr LC50 prediction value of 1.394 mg/L (based on estimated log Kow of 4.046) and 3.367 mg/L (based on measured log Kow of 3.6) are considered adequate for classification and labelling purposes and /or risk assessment.
- The predicted value of 1.394 mg/L is considered conservative and worst case given that it is based on an estimated Log Kow (4.046) which is significantly higher than the measured log Kow (3.6) and given that the measured data for fish and algal inhibition more closely match the predicted values based on measured log Kow (Table 1).

More detailed information is provided in the attached QPRF file.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Remarks:

See attached QMRF and QPRF documents for full discussion of the validity of the method

Conclusions:

The substance, SUPER MUGUET, was predicted to have a daphnid 48-hr LC50 of 1.4-3.4 mg/L. The result is relevant for classification and risk assessment.