Registration Dossier

Administrative data

Endpoint:
long-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2019-02-25 to 2019-02-25
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:
The QPRF and the QMRF are available and attached as background material.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2019
Report Date:
2019

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)
Deviations:
yes
Remarks:
QSAR model
Principles of method if other than guideline:
The chronic toxicity to fish was determined using a validated QSAR for the Mechanism of Action (MechoA) in question (MechoA 1.1, i.e. non-polar narcosis) (Bauer et al., 2018). The QSAR is based on validated data for a training set of 27 chemicals derived from 32-day test on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Sampling and analysis

Analytical monitoring:
not required
Details on sampling:
Not applicable.

Test solutions

Vehicle:
not specified
Details on test solutions:
Not applicable.

Test organisms

Test organisms (species):
other: Danio rerio, Pimephales promelas, Oryzias latipes, Jordanella floridae
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.

Study design

Test type:
other: For linear regression derivation, preferentially results from a flow-through test were used. However semi-static with daily renewal of test solutions and the control was accepted (preferably accompanied by analytical measurements over the study period).
Water media type:
freshwater
Limit test:
no
Remarks on exposure duration:
Only results from a test duration of 28 to 32 days were used for for linear regression derivation.
Post exposure observation period:
Not applicable.

Test conditions

Hardness:
Not applicable.
Test temperature:
The temperatures varied from approximately 25 +/- 2°C.
pH:
Test results were taken from studies with measured pHs between 6.0 - 8.5.
Dissolved oxygen:
Not applicable.
Salinity:
Not applicable.
Conductivity:
Not applicable.
Nominal and measured concentrations:
Not applicable.
Details on test conditions:
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

Results and discussion

Effect concentrations
Key result
Duration:
32 d
Dose descriptor:
EC10
Effect conc.:
0.058 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
other: Growth and/or Reproducunbility
Remarks on result:
other: 95% CL
Remarks:
0.039-0.087
Details on results:
None.
Results with reference substance (positive control):
Not applicable.
Reported statistics and error estimates:
95 % CL [0.039-0.087] QSAR statistical parameters are given in the QMRF and QPRF

Any other information on results incl. tables

   Evaluation and statistics

The evaluation of the effects was based on regression line derived from a training set of 27 chemicals with MechoA 1.1 using a validated dataset on subcooled solubility versusthe maximum acceptable toxicant concentration (MATC)based on growth or reproducibility of fish following the methodology outlined inECETOC (2013)andThomaset al.(2015). In brief, the algorithm used was an improved version of that used by ECETOC for non-polar narcotic compounds which wasthen validated using an external test set.The modelling algorithm was derived using a simple linear regression with the following general equation:

logEC10 = a X logWater Solubility +b

The correlation coefficient R2and Root Mean Standard Error (RMSE) values for this model were 0.9521 and 0.2525, respectively. As discussed in theQSAR Model Reporting Format, closer the R2is to 1 and lower the RMSE values are, better is the goodness-of-fit for the model. Therefore, the model was considered as reliable for providing accurate predictions falling within its applicability domain.Further statistical evidence of high prediction accuracy are provided in the QSAR Prediction Reporting Format (QPRF) for the substance provided in Annex I and the QSAR Model Reporting Format (QMRF)(KREATiS, 2019).Other MechoAs are being added to the KREATiS database as sufficient evidence for high accuracy predictions becomes available.

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Remarks:
The substance falls into applicability domains of the model QSAR
Conclusions:
The test item falls within the applicability domain of the model and can therefore be considered a reliably prediction for chronic toxicity (32d-EC10) to fish. Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.
The 32d-EC10 of the test item to fish was predicted as 0.058 mg/L.
95% confidence interval (α = 0.05): 0.039 – 0.087 mg/L.

Based on the results of this study, delta-3-carene is classified hazardous to the aquatic environment under Regulation (EC) No 1272/2008 (CLP) - Chronic Category 2.
Executive summary:

A QSAR model model was used to calculate the chronic toxicity of test item delta-3 -carene to fish. 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 Guideline for Testing of Chemicals No. 210, "Fish, Early-life Stage Toxicity Test"(OECD, 2013). The criterion predicted was the EC10 (10% Effective Concentration), a concentration which is expected to cause an effect of 10% on on growth or reproducibility within a period of 32 days.

The result below is the chronic toxicity value anticipated during a 32-day EC10 study on fish. The 32-day EC10 is calculated as follows:

 

Time (d)

EC10 (mg test item.L-1)

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

32

0.058

0.039 – 0.087