6,8-dimethylnon-7-enal

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:

October 18th, 2019

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
iSafeRat® toolbox – in Silico Algorithms For Environmental Risk And Toxicity version 2.4

2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.8

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=CCCCCC(C)C=C(C)C
The toxicity of the test item was predicted using the iSafeRat® Ecotox module providing the Subcooled Liquid Water Solubility (SLWS) as the input. The SLWS has been derived using a holistic approach: 40.2 mg/L (or -3.622 in log (mol/L)).

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Deviations:

not applicable

Remarks:

QSAR model

Principles of method if other than guideline:

The purpose of this QSAR model is to accurately predict the acute toxicity to fish as would be expected in a laboratory experiment following the OECD Guideline 203 and EC method C.1 for specific named modes of action. The model provides an in silico prediction for the 96-hour LC50 value that can effectively be used in place of an experimentally derived 96-hour LC50 value. The regression based method used to achieve this has been fully validated following the OECD (2004) recommendations.

GLP compliance:

no

Remarks:

QSAR model

Specific details on test material used for the study:

- log KOW = 3.87 (Phytosafe, 2008, EU Method A.8, Flask Method)
- Water Solubility 40.2 mg/L (KREATiS, 2019)
- Mechanism of action: MechoA 3.1: hard electrophiles (Bauer et al., 2018)

Analytical monitoring:

no

Details on sampling:

not applicable

Vehicle:

no

Details on test solutions:

not applicable

Test organisms (species):

other: Danio rerio, Oncorhynchus mykiss, Lepomis macrochirus, Pimephales promelas, Oryzias latipes, Leuciscus idus

Details on test organisms:

No difference in terms of toxic mechanism of action between fish freshwater species is expected. Any observed differences may be attributed to lifestyle related parameters (e.g. relative differences in storage lipid content between species) and relative duration of study versus bodysize rather than to a specific toxic mechanism causing species differences.

Test type:

other: QSAR model

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Remarks on exposure duration:

Only results from a test duration of 96 hours were included in the training set of the model.

Post exposure observation period:

None

Hardness:

The QSAR is based on data from studies performed at acceptable hardness to ensure control survival.

Test temperature:

The temperatures varied from approximately 14 to 25 °C depending on the fish species used to construct the algorithm. While it is recognized that this may contribute to some extent to the variability of the LC50 values found in experimental data, KREATiS has not observed a clear trend suggesting that normalization to temperature would necessarily improve the algorithm (say for trout as opposed to warm water species like fathead minnow for example) for monoconstituents.

pH:

Test results were taken from studies with measured pHs between 6.0 - 8.5.

Dissolved oxygen:

The QSAR is based on data from reliable studies performed at acceptable oxygen concentrations (generally >60%).

Salinity:

Not applicable

Conductivity:

No data

Nominal and measured concentrations:

Studies were used only where sufficient evidence was presented to determine that the stubstance was stable under test conditions (i.e. maintened within ± 20 % of the nominal) or, if not, the result was based on measured concentrations as geometric
mean.

Details on test conditions:

A variety of test designs were accepted: Preferentially results from semi-static experiments with daily renewal of test solutions and the control or from flow-through tests were used. However, for stable, low volatility substances a static design was accepted (preferably accompanied by analytical measurements over the study period). For suspected volatile substances only tests performed in closed vessels were accepted unless accompanying analytical monitoring proved such a design was not necessary.

Reference substance (positive control):

not required

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

1.9 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95%CL: 0.93 - 3.9 mg/L

Details on results:

The test item falls within the applicability domain of the model and can therefore be considered a reliably 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.

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

95% confidence interval (α = 0.05): 0.93 – 3.9 mg/L.
QSAR statistical parameters are given in the QMRF and the QPRF

Sublethal observations / clinical signs:

Analysis of the Applicability Domain

Descriptor domain:

The Subcooled Liquid Water Solubility value (40.2 mg/L or -3.622 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 -5.15 to -0.76.

Structural fragment domain:

All chemical groups within the molecular structure are taken into account by the model.

Mechanistic domain:

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 an aldehyde is expected to exert a MechoA 3.1 and can be taken into account by the model.

See QMRF in "attached background material".

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 1.9 mg/L.
95% confidence interval (α = 0.05): 0.93 – 3.9 mg/L.

Executive summary:

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 principles 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, 1992), 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 96hours.

The acute toxicity to fish was determined using a validated QSAR for the Mechanism of Action (MechoA) in question (MechoA 3.1, i.e. hard electrophiles as aldehyde) (Bauer et al., 2018). The QSAR is based on validated data for a fully validated training set of 5 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 was statistically determined as having an R2 of 0.9741 and Root Mean Standard Error (RMSE) value of 0.1390.

.

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 1.9 mg/L.

95% confidence intervals (α = 0.05): 0.93 – 3.9 mg/L.

Description of key information

iSafeRat® High-Accuracy-Quantitative Structure-Activity Relationship, KREATIS, 2019 :

96h-LC50 = 1.9 mg/L (95% confidence interval: 0.93 – 3.9 mg/L)

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

1.9 mg/L

Additional information

A QSAR prediction was performed to assess the acute toxicity of the registered substance to fish. This QSAR has been validated to be compliant with the OECD recommendations for QSAR modelling (OECD, 2004) and predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following OECD Guideline 203. 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 acute toxicity to fish was determined using a validated QSAR for the Mechanism of Action (MechoA) in question (MechoA 3.1, i.e. hard electrophiles such as aldehydes) (Bauer et al., 2018). The QSAR is based on a small but fully validated training set with an R2 of 0.9741 and Root Mean Standard Error (RMSE) value of 0.1390.

derived from a 96-hour test on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period.

The result below is the toxicity value predicted for a 96-hour LC50 study on fish based on measured concentrations.

The 96h-LC50 of the test item to fish was predicted as 1.9 mg/L.

95% confidence interval (α = 0.05): 0.93 – 3.9 mg/L