(4E)-4-(3,3,4-trimethylcyclopentylidene)butanal

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:

April 15, 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
iSafeRat® holistic HA-QSAR v1.9

2. MODEL (incl. version number)
iSafeRat® fishLC50 v1.9

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC1CC(=CCCC=O)CC1(C)C
Water solubility = 50.3 mg/L (LPL, 2020)

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 ACUTE TOXICITY TO FISH (96-HOUR LC50) was determined using the iSafeRat® fishLC50, a validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 3.1, i.e. hard electrophiles) (Bauer et al., 2018). The QSAR is based on validated data for a 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.

GLP compliance:

no

Remarks:

Not applicable: QSAR model

Specific details on test material used for the study:

- Mechanism of action : MechoA 3.1: hard electrophiles (Bauer et al., 2018)
- Water solubility : 50.3 mg/L (LPL, 2020)

Analytical monitoring:

not required

Remarks:

QSAR model

Details on sampling:

Not applicable

Vehicle:

no

Details on test solutions:

Not applicable

Test organisms (species):

other: Results from the following species were used in the regression: 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.

Post exposure observation period:

Not applicable

Hardness:

Not applicable

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. Nevertheless, this is a recognized area for further research by KREATiS.

pH:

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

Dissolved oxygen:

The dissolved oxygen concentration was more than 60% of the air-saturation value throughout the duration of the test. In exceptional cases where studies with oxygen concentrations lower than 60% were used, all aspects of the study were thoroughly evaluated in order to satisfy the evaluator that the effects found were not due to reduced oxygen concentration (i.e. the study would correctly receive a Klimisch score of 2 under the REACH Regulation (REACH, 2006).

Salinity:

Not applicable

Conductivity:

Not applicable

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

Remarks:

QSAR model

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

2.2 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95CI: [1.1 ; 4.5] mg/L

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

95% confidence interval (α = 0.05): 1.1-4.5 mg/L. QSAR statistical parameters are precised in the QMRF, in the attached background material.

Sublethal observations / clinical signs:

No additional information

Validity criteria fulfilled:

yes

Remarks:

The substance falls into the applicability domains of the QSAR model.

Conclusions:

The QSAR model used to achieve the study has been fully validated following the OECD recommendations (OECD, 2004). The test item falls within the applicability domain of the model and was therefore reliably predicted for its ACUTE TOXICITY TO FISH (96-HOUR LC50). Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

The ACUTE TOXICITY TO FISH (96-HOUR LC50) of the test item was predicted as 2.2 mg/L.
95% confidence interval (α = 0.05): 1.1 – 4.5 mg/L.

Executive summary:

A Quantitative Structure Activity Realtionship (QSAR) model was used to calculate the ACUTE TOXICITY TO FISH (96-HOUR LC50) for 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 ACUTE TOXICITY TO FISH (96-HOUR LC50) was determined using the iSafeRat® fishLC50, a validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 3.1, i.e. hard electrophiles) (Bauer et al., 2018). The QSAR is based on validated data for a 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 test item falls within the applicability domain of the model and was therefore reliably predicted for its ACUTE TOXICITY TO FISH (96-HOUR LC50). Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

The ACUTE TOXICITY TO FISH (96-HOUR LC50) of the test item was predicted as 2.2 mg/L.

95% confidence interval (α = 0.05): 1.1 – 4.5 mg/L.

Description of key information

iSafeRat® High-Accuracy-Quantitative Structure-Activity Relationship, KREATIS, 2020 :

96h-LC50 = 2.2 mg/L (95% confidence interval: 1.1 – 4.5 mg/L)

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

2.2 mg/L

Additional information

One QSAR prediction is available to assess the short-term toxicity of the registered substance to fish.

This QSAR prediction (KREATiS, 2020) was considered as reliable and was used as the key data. The QSAR model 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 acute toxicity to fish (96h-LC50 value) was determined using a validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 3.1, i.e. hard electrophiles) (Bauer et al., 2018). The QSAR model is based on validated data for a 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 test item falls within the applicability domain of the model and was therefore reliably predicted for its acute toxicity to fish. Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

The 96h-LC50 of the registered substance to fish was predicted at 2.2 mg/L (95% CI: 1.1 - 4.5 mg/L).