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Short-term toxicity to fish

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Reference
Endpoint:
short-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
key study
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:
1. SOFTWARE
EPISuite v4.11

2. MODEL (incl. version number)
ECOSAR v1.11

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES : O(CCCCCC)CCCCCC
CHEM : Hexane, 1,1 -oxybis-
CAS Num: 000112-58-3
MOL FOR: C12 H26 O1
MOL WT : 186.34
Wat Sol: 2.874 (mg/L, EPISuite WSKowwin v1.43 Estimate)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
ECOSAR had been utilized by the scientific community for prediction of aquatic toxicity since the 1990’s. While developed by the US EPA, the program underwent an independent peer review as a principles established for quantitative structure-activity relationship ((Q)SAR) validation. As of 2011, ECOSAR was the subject of 20 peer reviewed publications regarding its validation and performance. Also ECOSAR has been incorporated into the OECD Toolbox and was considered a top performer for use in profiling chemicals. Inclusion in the OECD toolbox requires specific documentation, validation and acceptability criteria and subjects ECOSAR to international use, review, providing a means for receiving additional and on-going input for improvements. ECOSAR is listed as one of the QSARs tools for use in predicting aquatic toxicity values in the Guidance on information requirements and chemical safety assessment Chapter R.10: Characterisation of dose [concentration]-response for the environment and Chapter R.6: QSARs and grouping of chemicals.
In summary, ECOSAR has had its scientific validity established repeatedly.

5. APPLICABILITY DOMAIN
ECOSAR’s training set generally includes chemicals that had log Kow’s between -3 and 8 with molecu
lar weights less than 1000. While the applicability domain of ECOSAR is considered to be larger tha
n just the training set, the log Kow (4.978) and molecular weight (186.34) fall within the range of the
training set values and is thus considered within the applicability domain. The log Kow (4.978) is also
lower than the maximum log Kow for the neutral organics equation (6.4).

6. ADEQUACY OF THE RESULT
ECOSAR’s Neutral Organic’s (Baseline Toxicity) model uses the following equation for calculation of acute aquatic toxicity to fish:

Organism Endpoint Equation
Fish 96 hr LC50 Log LC50 (mmol/L) = -0.8981(log Kow) + 1.7108

The equation has the following statistics:
Number of substances = 296
Correlation coef (r2) = 0.878

This correlation coefficient indicate the ECOSAR model calculates results that are equivalent to those generated experimentally and are, hence, adequate for the purpose of classification and labelling and/or risk assessment.

Furthermore, documentation and validity of the ECOSAR QSAR models are provided in the following references:
Clements, RG, Nabholz, JV and Zeeman, R. 1996. Estimating Toxicity of Industrial Chemicals to Aquatic Organisms Using Structure-activity Relationships.
ECHA (2008) “Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals”.
ECHA (2008) “Guidance on information requirements and chemical safety assessment Chapter R.10: Characterisation of dose [concentration]-response for the environment”.
Mayo-Bean, K, Nabholz, JV, Clements, R, Zeeman, M, Henry, T, Rodier, D, Moran, K, Meylan, WM and Ranslow, P. 2011a. Methodology Document for the Ecological Structure-Activity Relationship Model (ECOSAR) Class Program.
Mayo-Bean, K, Nabholz, JV, Meylan, WM, Howard, PH and Moran-Bruce, K. 2011b. Operation Manual for the Ecological Structure-Activity Relationship Model (ECOSAR) Class Program.
Principles of method if other than guideline:
- Software tool(s) used including version: EPISuite v4.11
- Model(s) used: ECOSAR v1.11
- Model description: see field 'Justification for type of information'
- Justification of QSAR prediction: see field 'Justification for type of information'
Specific details on test material used for the study:
OTHER SPECIFICS:
SMILES : O(CCCCCC)CCCCCC
CHEM : Hexane, 1,1 -oxybis-
CAS Num: 000112-58-3
MOL FOR: C12 H26 O1
MOL WT : 186.34
Log Kow: 4.978 (EPISuite Kowwin v1.68 Estimate)
Wat Sol: 2.874 (mg/L, EPISuite WSKowwin v1.43 Estimate)
Key result
Duration:
96 h
Dose descriptor:
LC50
Effect conc.:
0.324 mg/L
Conc. based on:
test mat.
Basis for effect:
mortality
Remarks on result:
other: QSAR
Validity criteria fulfilled:
yes
Conclusions:
The ECOSAR predicted toxicity values are considered valid and fit for purpose.
Executive summary:

A reliable QSAR model (Ecological Structure-Activity Relationship (ECOSAR) version 1.11) was used to predict the acute toxicity of dihexyl ether to fish. The 96 hour LC50 was 0.324 mg/L for the neutral organic class.

Description of key information

In the absence of experimental data, a reliable QSAR model (Ecological Structure-Activity Relationship (ECOSAR) version 1.11) was used to predict the acute toxicity of dihexyl ether to fish. The 96 hour LC50 was 0.324 mg/L for the neutral organic class.

Key value for chemical safety assessment

LC50 for freshwater fish:
0.324 mg/L

Additional information