Bis[(3,4-epoxycyclohexyl)methyl] adipate

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

13 April 2018

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:

SOFTWARE
EPI Suite Version 4.11

MODEL
ECOSAR Version 1.11.

SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C(OCC(CC(O1)C1C2)C2)CCCCC(=O)OCC(CC(O3)C3C4)C4

SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
-The structure-activity relationships (SARs) presented in this program are used to predict the aquatic toxicity of chemicals based on their similarity of structure to chemicals for which the aquatic toxicity has been previously measured. Most SAR calculations in the ECOSAR Class Program are based upon the octanol/water partition coefficient (Kow). Various surfactant SAR calculations are based upon the average length of carbon chains or the number of ethoxylate units.
- SARs have been used by the U.S. Environmental Protection Agency since 1981 to predict the aquatic toxicity of new industrial chemicals in the absence of test data. The acute toxicity of a chemical to fish (both fresh and saltwater), water fleas (daphnids), and green algae has been the focus of the development of SARs, although for some chemical classes SARs are available for other effects (e.g, chronic toxicity and bioconcentration factor) and organisms (e.g., earthworms). SARs are developed for chemical classes based on measured test data that have been submitted by industry or they are developed by other sources for chemicals with similar structures, e.g., phenols. Using the measured aquatic toxicity values and estimated Kow values, regression equations can be developed for a class of chemicals. Toxicity values for new chemicals may then be calculated by inserting the estimated Kow into the regression equation and correcting the resultant value for the molecular weight of the compound.
- There are currently 130 chemical classes programmed into ECOSAR. For those 130 classes, there are a total of 440 QSARs based on publicly available experimental data and confidential studies collected under the EPA New Chemicals Program. For each class, a standard EPA New Chemicals Program aquatic toxicity profile will be created using available QSARs and/or alternate SAR approaches and professional judgment. This standard profile typically contains 3 acute values, and 3 chronic values for fish, daphnia, and green algae. In an effort to complete a profile for each class, 173 endpoints have been estimated using alternative approaches such as acute-to-chronic ratios and substitute QSARs based on scientific judgment.
- ECOSAR estimates log Kow values using the US EPA's KOWWIN Program. Information about the KOWWIN Program its log Kow estimations are available in the on-line KOWWIN Help File.
- The ECOSAR Class Program is a computerised version of the ECOSAR analysis procedures as currently practiced by the Office of Pollution Prevention and Toxics (OPPT). It has been developed within the regulatory constraints of the Toxic Substances Control Act (TSCA). It is a pragmatic approach to SAR as opposed to a theoretical approach.

APPLICABILITY DOMAIN
The fish 96-h LC50 values used to develop this SAR were measured and the octanol water partition coefficients (Kow) were calculated using the computer program, KOWWIN (Version 1.67).  The SAR equation used to estimate toxicity is:
Log 96-h LC50 (mmol/L) = -0.5717 (log Kow) + 0.2768
The LC50 is in millimoles per liter (mM/L); N = 81 + 16; and the Coefficient of Determination (R2) = 0.786.  To convert the LC50 from mM/L to mg/L, multiply by the molecular weight of the ester.
Maximum Kow:  5.0
Maximum MW: 1000
Limitations: If the log Kow value is greater than 5.0, or if the compound is solid and the LC50 exceeds the water solubility by 10X, no effects at saturation are predicted.
The test material is therefore within the applicability domain.

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Version / remarks:

May/July 2008

Deviations:

no

Principles of method if other than guideline:

Calculation

GLP compliance:

no

Specific details on test material used for the study:

- Molecular weight: 366.46

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

3.929 mg/L

Nominal / measured:

estimated

Conc. based on:

test mat.

Basis for effect:

other: calculation

Remarks on result:

other: Calculated value excceds the water solubility of the test material (<2.0 mg/L).

Sublethal observations / clinical signs:

--------------------------------------

ECOSAR v1.11 Class-specific Estimations

--------------------------------------

Epoxides, Poly

Esters

Predicted

ECOSAR Class Organism Duration End Pt mg/L (ppm)

=========================== ==================

Epoxides, Poly : Fish 14-day LC50 0.742

Epoxides, Poly : Daphnid 48-hr LC50 1.929

Epoxides, Poly : Fish ChV 0.022 !

Epoxides, Poly : Daphnid ChV 0.150 !

Esters : Fish 96-hr LC50 3.929 *

Esters : Daphnid 48-hr LC50 6.681 *

Esters : Green Algae 96-hr EC50 2.112

Esters : Fish ChV 0.199

Esters : Daphnid ChV 2.663 *

Esters : Green Algae ChV 0.996

Esters : Fish (SW) 96-hr LC50 5.328 *

Esters : Mysid 96-hr LC50 2.079

Esters : Fish (SW) ChV 1.071

Esters : Mysid (SW) ChV 3.341 *

Esters : Earthworm 14-day LC50 1186.515 *

=========================== ==================

Neutral Organic SAR : Fish 96-hr LC50 6.215 *

(Baseline Toxicity) : Daphnid 48-hr LC50 4.196 *

Green Algae 96-hr EC50 6.399 *

Fish ChV 0.745

Daphnid ChV 0.663

Green Algae ChV 2.465 *

Note:

* = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

! = exclamation designates: The toxicity value was estimated through application of acute-to-chronic ratios

Validity criteria fulfilled:

not applicable

Conclusions:

The 96 hour LC50 was calculated to be 3.929 mg/L which exceeds the water solubility of the test material (<2.0 mg/L).

Executive summary:

The LC50 of the test material to fish was calculated using ECOSAR Version 1.11.

The QSAR gives a predicted LC50 value of 3.929 mg/L which exceeds water solubility of the test material, therefore the test material is unlikely to reach the levels of solubility which would cause classification.

This has been observed in both daphnia and algae studies and therefore is anticipated to occur again in the fish study.

Description of key information

The LC50 of the test material to fish was calculated using ECOSAR Version 1.11.

The QSAR gives a predicted LC50 value of 3.929 mg/L which exceeds water solubility of the test material, therefore the test material is unlikely to reach the levels of solubility which would cause classification.

This has been observed in both daphnia and algae studies and therefore is anticipated to occur again in the fish study.