Calcium di(octanoate)

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:

January 8 2020

Reliability:

1 (reliable without restriction)

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
Validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 5.2, i.e. proton release of carboxylic acids) (Bauer et al., 2018)

2. MODEL (incl. version number)
MechoA 5.2.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
IUPAC name: calcium dioctanoate
SMILES: CCCCCCCC(=O)[O-].CCCCCCCC(=O)[O-].[Ca+2]
Substance type: monoconstituent
CAS-No.: 6107-56-8
Molecular formula: C16H30CaO4
Molecular weight: 326.5 g/mol
Description, at 25°C: solid
Melting point (if solid): not determined, the substance decomposes before melting (ECHA dossier, 2020)

NB: Since the test item is an organic salt wich dissociates into aqueous solute, only the carboxylate (i.e. octanoate) has been considered for the prediction. Indeed in experimental tests for organic salts, the concentration of the counter-ion is usually not measured and only the organic ion (or its neutral form) is monitored. Moreover the medium used to conduct ecotoxicological assays is buffered at pH between 6 – 9 where there is an equilibrium between non-ionized form (free acid) and ionised form (carboxylate), and both are present in the test medium, no matter if at first the acid or a salt of it was introduced. In fact, at this pH, most of the substance will be in its ionized form (carboxylate). Consequently, the toxicity of the test item predicted in this study is based on the octanoic acid.

IUPAC name: octanoic acid
SMILES: CCCCCCCC(=O)O
Substance type: monoconstituent
CAS-No. 124-07-2
Molecular formula: C8H16O2
Molecular weight: 144.21 g/mol
Description, at 25°C: liquid
log KOW, at 25°C: 3.0 for the neutral form (KREATiS – internal study, 2020)
Water Solubility, at 25°C: 716 mg/L for the neutral form (KREATiS – internal study, 2020)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The studies used in the dataset were considered valid under the OECD guideline and REACH regulation (European Parliament and European Union Council, 2006) (i.e. Klimisch score 1 or 2) by registrants of the substances included in the training and test sets were revalidated by KREATiS and the critical parameters of the study were considered to be within acceptable limits.

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
- Descriptor domain: The Subcooled Liquid Water Solubility value (716 mg/L or -2.304 in log (mol/L)) given as the input to the Ecotox module of the iSafeRat® Holistic HA-QSAR falls within the descriptor domain of the model between a log water solubility (in log (mol/L)) of -3.55 to 2.00.
- Structural and mechanistic domains: All chemical groups within the molecular structure are taken into account by the model.
Currently, the ecotoxicity module of the iSafeRat® Holistic HA-QSAR can reliably predict the aquatic toxicity for chemicals with the following mechanisms of action of toxicity (MechoA):
• non-polar narcosis (MechoA 1.1)
• polar narcosis of alkyl-/alkoxy-phenols (MechoA 1.2)
• polar narcosis of aliphatic amines (MechoA 1.2)
• cationic narcosis of quaternary ammoniums (MechoA 1.3)
• mono-/poly-esters whose hydrolysis products are narcotics (MechoA 2.1)
• hard electrophile reactivity (MechoA 3.1)
• RedOx cycling of primary thiols (MechoA 4.4)
• Proton release of carboxylic acids (MechoA 5.2)
The MechoA of molecules is predicted directly from the structure. The test item as a carboxylic acid is expected to exert a MechoA 5.2 and can be taken into account by the model.

6. ADEQUACY OF THE RESULT
This QSAR model has been validated to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) and 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. 203, "Fish Acute Toxicity Test" (OECD, 2019), referenced as Method C.1 of Commission Regulation No. 440/2008 (European Commission, 2008).

In May 2015, the earlier version of this QSAR Model Report Format (QMRF) (v1.3) was peer-reviewed by the Joint Research Centre, ISPRA, Italy and was added to their QMRF inventory with the following QMRF identifier: Q19-46-51-448.
Version 1.4 includes a small change to the log KOW of the ether contribution improving the accuracy of the log KOW prediction of this group of chemicals.
Version 1.5 includes updates to take into account alkyl/alkoxyphenols.
Version 1.6 includes updates about esters and aldehydes.
Version 1.7 includes updates about thiols.
Version 1.8 includes updates about carboxylic acids, amines and ammoniums.
http://qsardb.jrc.ec.europa.eu/qmrf/

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Version / remarks:

OECD (2004). Principles for the validation, for regulatory purposes, of (Quantitative) Structure Activity-Relationship Models

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

GLP compliance:

not specified

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.001 mol/L

Nominal / measured:

meas. (not specified)

Remarks on result:

other: 95% confidence limits (mol test item.L-1)

Remarks:

3.71E-04 – 1.01E-03

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

100 mg/L

Remarks on result:

other: 95% confidence limits (mg test item.L-1)

Remarks:

61 – 160

Details on results:

The initial result is the toxicity value anticipated during a 96-hour LC50 study on fish based on measured concentrations for the OCTANOIC ACID.
The corrected 96-hour LC50 for the test item takes into account the molarity of the target (i.e. OCTANOATE) into the test item (i.e. CALCIUM DI(OCTANOATE) following this equation :

LC50 (test item) =LC50 (target)/2

Then, the toxicity is converted into mg/L by taking into account the molecular weight of the test item. This provides a final 96 h result of 100 mg/L.

Validity criteria fulfilled:

yes

Conclusions:

The test item falls within the applicability domain of the model and can therefore be considered a reliable prediction for acute toxicity (96h-LC50) to fish. Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.
The 96h-LC50 of the test item to fish was predicted as 100 mg/L.
95% confidence interval (α = 0.05): 61 – 160 mg/L.

Executive summary:

Introduction. A Quantitative Structure Activity Realtionship (QSAR) model was used to calculate the acute toxicity to fish exposed to the test item. This QSAR model has been validated to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) and 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. 203, "Fish Acute Toxicity Test" (OECD, 2019), referenced as Method C.1 of Commission Regulation No. 440/2008 (European Commission, 2008). The criterion predicted was the LC₅₀ (Median Lethal Concentration), a statistically derived concentration which is expected to cause mortality in 50% of test animals within a period of 96 hours.

 Methods. The acute toxicity to fish was determined considering the chemical species expected to cause the toxicity of the test item. A validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 5.2, i.e.proton release of carboxylic acids) (Baueret al., 2018) has been used. The QSAR is based on validated data for a training set of 11 chemicals derived from 96-hour test on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period. The QSAR result has been corrected taking into account the molarity of the test item and its molecular weight.

Results. The result below is the toxicity value anticipated during a 96-hour LC₅₀ study on fish based on measured concentrations.

The 96h-LC50 of the test item to fish was predicted as 100 mg/L.

95% confidence interval (α = 0.05): 61 – 160 mg/L.

Description of key information

The 96h-LC50 of the test item to fish was predicted as 100 mg/L. 95% confidence interval (α = 0.05): 61 – 160 mg/L.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

100 mg/L

Additional information

A Quantitative Structure Activity Realtionship (QSAR) model was used to calculate the acute toxicity to fish exposed to the test item. This QSAR model has been validated to be compliant with the OECD recommendations for QSAR modeling(OECD, 2004)and 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. 203, "Fish Acute Toxicity Test"(OECD, 2019), referenced as Method C.1 of Commission Regulation No. 440/2008(European Commission, 2008). The criterion predicted was the LC₅₀(Median Lethal Concentration), a statistically derived concentration which is expected to cause mortality in 50% of test animals within a period of 96 hours.

The test item falls within the applicability domain of the model and can therefore be considered a reliable prediction for acute toxicity (96h-LC50) to fish. Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

The 96h-LC50 of the test item to fish was predicted as 100 mg/L.

95% confidence interval (α = 0.05): 61 – 160 mg/L.