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Ecotoxicological information

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

Referenceopen allclose all

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 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 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

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 concentrationsopen allclose all
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
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
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
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.