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Short-term toxicity to fish

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Endpoint:
short-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
key study
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. SOFTWAREiSafeRat® toolbox – in Silico Algorithms For Environmental Risk And Toxicity version 2.22. MODEL (incl. version number)iSafeRat® holistic HA-QSAR v1.63. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODELC1C(CCC)COC(=O)C14. SCIENTIFIC VALIDITY OF THE (Q)SAR MODELSee attached QMRF5. APPLICABILITY DOMAINSee attached QPRF6. ADEQUACY OF THE RESULTSee attached QPRF
Qualifier:
equivalent or similar to
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 was determined using a validated QSAR for the Mode of Action in question (esters). The QSAR is based on validated data for a training set of 34 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
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL- Source and lot/batch No.of test material: not applicable- Expiration date of the lot/batch: not applicable- Purity test date: not applicableSTABILITY AND STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: not applicable- Stability under test conditions: not applicable- Solubility and stability of the test substance in the solvent/vehicle: not applicable- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: not applicable
Analytical monitoring:
no
Details on sampling:
not applicable
Vehicle:
no
Details on test solutions:
not applicable
Test organisms (species):
other: fish spp.
Details on test organisms:
not applicable
Test type:
other: QSAR model
Water media type:
freshwater
Limit test:
no
Total exposure duration:
96 h
Remarks on exposure duration:
not applicable
Post exposure observation period:
not applicable
Hardness:
The QSAR model is based on data from studies performed at acceptable hardness to ensure control survival.
Test temperature:
The QSAR model is based on data from studies performed at between 14 - 25 °C (depending on the species considered).
pH:
The QSAR model is based on data from studies performed at pH between 6.0 - 9.0.
Dissolved oxygen:
The QSAR model is based on data from studies performed at acceptable oxygen concentrations (generally >60%).
Salinity:
The QSAR model is based on data from studies performed on freshwater species.
Conductivity:
No data
Nominal and measured concentrations:
The QSAR is based on data studies performed using measured concentrations or with acceptable stability.
Details on test conditions:
not applicable
Reference substance (positive control):
no
Remarks:
QSAR model
Key result
Duration:
96 h
Dose descriptor:
LC50
Effect conc.:
71 mg/L
Conc. based on:
test mat.
Basis for effect:
mortality
Remarks on result:
other: 95CI [58 - 88] mg/L
Details on results:
- Descriptor domain: The water solubility value given as the input to the Ecotox module of the iSafeRat® Holistic HAQSAR falls within the descriptor domain of the model between a log water solubility (in log (mol/L)) of -4.79 to 1.69.- Structural fragment domain: All chemical groups within the molecular structure are taken into account by the model.- Mecanistic domain, if relevant: Currently, the ecotoxicity module of the iSafeRat® Holistic HA-QSAR can reliably predict the acute aquatic toxicity for mono- and poly-esters based on the chemical structure. The test item as a lactone (cyclic ester) is expected to fall on the mono-ester regression line.- Considerations on structural analogues: iSafeRat® Holistic HA-QSAR is mainly based on the thermodynamic relationship between water solubility and the aquatic toxicity. This model was constructed using high quality data for water solubility and acute toxicity to fish for 34 esters compounds.
Results with reference substance (positive control):
Not applicable
Reported statistics and error estimates:
95% confidence interval (α = 0.05): 58 - 88 mg/LQSAR statistical parameters are given in the QMRF and QPRF.

No data

Validity criteria fulfilled:
yes
Conclusions:
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.
Executive summary:

The acute toxicity to fish was determined using a validated QSAR for the Mode of Action in question (esters). The QSAR is based on validated data for a training set of 32 esters 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 acute toxicity to fish of the test item has been investigated using a QSAR model that predicts fish mortality in an OECD 203 study.

The test item falls falls within the applicability domain of the model.

The 96h-LC50 based mortality was predicted as 71 mg test item/L

This toxicity study is acceptable and can be used for that endpoint.

Results synopsis

Test type: QSAR model

LC50: 71 mg test item/L

95% Confidence Interval: 58 -88 mg test item/L

Endpoint:
short-term toxicity to fish
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2012-01-12 to 2012-08-23
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: The different test concentrations were not maintained within 80-120 %. The procedural average recovery was 46.9%. This lowrecovery renders the study invalid as less than the 70% minimum recovery value required for analytical validity.
Qualifier:
according to
Guideline:
OECD Guideline 203 (Fish, Acute Toxicity Test)
Deviations:
yes
Remarks:
The different test concentrations were not maintained within 80-120 %.
Qualifier:
according to
Guideline:
other: State Environmental Protecion Administration of China. The Guidelines for the Testing of Chemicals, 203 Fish Acute toxicity test. China environmental Science Press. 2004.
Deviations:
no
Qualifier:
according to
Guideline:
other: State Environmental Protection Administration of China. The guidelines for the testing of chemicals (HJ/T 153-2004). Beijing : China Environmental Science Press. 2004.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL- Batch No. : 1178999STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL- Storage condition of test material: Store in a cool place in original container and protect from sunlight and moisture.
Analytical monitoring:
yes
Details on sampling:
- Temperature, pH and dissolved oxygen of test solution of each test group were measured at 0h, 96h and 24h, 48h, 72h (before and after the renewal).- Concentrations (measured) : 5.206 mg/L, 8.142 mg/L, 13.15 mg/L, 21.54 mg/L and 35.06 mg/L.- Measurement of actual concentrations of test substance of blank control and five test groups were measured at 0h, 96h and 24h, 48h, 72h (before and after the renewal).
Vehicle:
not specified
Details on test solutions:
PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)- Method: Blank control : 3000 mL test water was directly added into the test container. Three replicates were prepared.Test substance group : 593 mL, 889 mL, 1333 mL, 2000 mL and 3000 mL of the saturation solution (LS) were taken into the test container, and then 2407 mL, 2111 mL, 1667 mL, 1000 mL and 0 mL of test water was added. - Controls:A blank control (test water without test substance) was run in parallel to the test concentrations.
Test organisms (species):
Danio rerio (previous name: Brachydanio rerio)
Details on test organisms:
TEST ORGANISM- Common name: Zebra fish- Strain: Brachydanio rerio- Source: fish supplied by Guangzhou Yang Shi Breeding farm- Length at study initiation (length definition, mean, range and SD): 24.57 mm +/- 1.92 mm- Feeding frequency during acclimation: Fish were fed daily, until 24 hours before the start of the test- Weight at study initiation (mean and range, SD): average weight = 0.174 g +/- 0.028ACCLIMATION- Acclimation period: 24 days- Acclimation conditions (same as test or not): Flow-through, under the same conditions of water quality (dechlorinated tap water), temperature 23 +/- 2 °C, light and dark period (14h light / 10h dark).- Health during acclimation (any mortality observed): 0% mortality was observed during 7 days before the start of the test.FEEDING DURING TEST- the fish were not fed during the exposure
Test type:
semi-static
Water media type:
other: dechlorinated tap water
Limit test:
no
Total exposure duration:
96 h
Post exposure observation period:
None
Hardness:
92.2 mg/L
Test temperature:
23 +/- 2 °C
pH:
8.26
Dissolved oxygen:
The test solutions were not aerated during the exposure. The dissolved oxygen concentration in the test solutions during the test was kept at least at 60 % of the air saturation value.
Salinity:
No data
Conductivity:
No data
Nominal and measured concentrations:
Five nominal concentrations : 19.8 % LS (of the saturation solution), 29.6 LS, 44.4 %, 66.7 % and 100 % LS Five measured concentrations : 5.206 mg/L, 8.142 mg/L, 13.15 mg/L, 21.54 mg/L and 35.06 mg/L.
Details on test conditions:
TEST SYSTEM - Material, size, headspace, fill volume: 3 L / test vessel - Aeration: No aeration - No. of organisms per vessel: 7 fish / test vessel - No. of vessels per concentration (replicates): 3 replicates per group - No. of vessels per control (replicates): 3 replicates of blank control OTHER TEST CONDITIONS - Photoperiod: 14 h light / 10 h dark - Light intensity: Artificial light of white fluoescent lamp EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Mortality and visible abnormality of the test fish were recorded at 3h, 24 h, 48 h, 72 h and 96 h after the start of the test. The dead fish were removed as soon as they were found. A fish was considered dead if there was no visible movement (e.g. gill movements) and if touching of the caudal peduncle produces no reaction. TEST CONCENTRATIONS - Test concentrations: 5.206 mg/L, 8.142 mg/L, 13.15 mg/L, 21.54 mg/L and 35.06 mg/L.
Reference substance (positive control):
no
Key result
Duration:
96 h
Dose descriptor:
LC50
Effect conc.:
30.4 mg/L
Nominal / measured:
meas. (geom. mean)
Conc. based on:
test mat.
Basis for effect:
mortality
Remarks on result:
other: 95 % confidence limit : 26.8 mg/L - 34.6 mg/L
Remarks:
Not recalculated to include significant recovery losses
Duration:
96 h
Dose descriptor:
LC0
Effect conc.:
5.206 mg/L
Nominal / measured:
meas. (geom. mean)
Conc. based on:
test mat.
Basis for effect:
mortality
Duration:
96 h
Dose descriptor:
LC100
Effect conc.:
> 35.06 mg/L
Nominal / measured:
meas. (geom. mean)
Conc. based on:
test mat.
Basis for effect:
mortality
Key result
Duration:
96 h
Dose descriptor:
LC50
Effect conc.:
65 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
mortality
Remarks on result:
other: recalculated to account for low recovery values during analysis
Details on results:
- Mortality of control: The cumulative mortality of blank control was 0% at the end of the test. - Abnormal responses: No abnormal response was observed in blank control. Observed abnormal responses during the test were reduced activity, overturn and loss of equilibrium, immobilized at the bottom and so on.
Results with reference substance (positive control):
None
Reported statistics and error estimates:
None

Table 1 : Cumulative mortality (%)

Nominal concentration    (% LS)     Number of test fish

             Cumulative mortality (%)

 3 h  24 h  48 h  72 h  96 h
Blank control   21  0   0   0   0  0
 19.8  21  0   0   0   0  0
 29.6  21   0   0   0   0  5
 44.4  21   0   0   0   5  5
 66.7  21   0   0   5  5  9
 100  21   0  24  33  33  67

Table 2 : Median lethal concentration (LC50) and the 95 % confidence limit

 Exposure duration  LC50 (mg/L)  95 % confidence limits
 24 h  -  -
 48 h  -  -
 72 h  -  -
 96 h  30.4  26.8 mg/L - 34.6 mg/L

- : The LC50 and 95 % confidence limits are not available

Validity criteria fulfilled:
no
Remarks:
The different test concentrations were not maintained within 80-120 %.
Conclusions:
Under the test conditions, the 96h-LC50 for the test item was 30.4 mg/L.
Executive summary:

The acute toxicity of the test item to Zebra fish (Brachydanio rerio) was conducted according to OECD Guideline 203, according to the Guidelines for the Testing of Chemicals, 203 Fish Acute toxicity test, China environmental Science Press (2004), and according to the guidelines for the testing of chemicals (HJ/T 153 -2004), China Environmental Science Press (2004).

The test item was tested at five nominal concentrations : 19.8 % LS (of the saturation solution), 29.6 % LS, 44.4 % LS, 66.7 % LS and 100 % LS. The five measured concentrations were : 5.206 mg/L, 8.142 mg/L, 13.15 mg/L, 21.54 mg/L and 35.06 mg/L.The test was semi-static and ran for 96 h. A blank control (test water without test substance) was run in parallel with the test concentrations. 7 fish were placed into each test vessel.

Analysis of the efficacy of the recovery of the sample (three replicates) revealed a procedural average recovery of 46.9 % (47.25 %, 45.00 %, 48.59 %). This is below the minimum recovery level accepted to consider the analytical method as valid. Furthermore,no attempt was made to justify the poor recovery or to correct the results according to the level of recovery. Analysis of test media revealed that the test item concentrations were not maintained within 80 - 120 % of the nominal values.

Under the test conditions, the 96h-LC50 for the test item was 30.4 mg/L, the highest concentration causing 0 % mortality (LC0) was 5.206 mg/L and the lowest concentration causing 100 % mortality (LC100) was greater than 35.06 mg/L (calculated based on the geometric mean of actual concentration of 100 % LS group). These concentrations were not corrected according to the recovery level. However, despite the invalidity of the test, a correction calculation is made here to extrapolate to the true LC50 value by using the formula 100/46.9 x 30.4 = 65.0 mg/L. This value is considered closer to the true LC50 than the reported value.

Description of key information

The acute toxicity to fish of the test item has been determined using a validated QSAR model for the Mode of Action in question (esters) that predicts fish mortality in an OECD 203 study and supported by a reliability-3 study on Zebra fish.

The 96h-LC50 based mortality was predicted as 71 mg test item/L by the QSAR model. 95% Confidence Interval: 58 -88 mg test item/L.

The reliability-3 study (OECD 203) gave the lowest fish 96h-LC50 value (30.5 mg/L) but the procedural average recovery was only 46.9%. Multipling this correction value (100/46.9 x 30.5) gives a 96h-LC50 value of 65.0 mg/L (considered the key value) which is very close to the predicted, validated QSAR value of 71 mg/L. For this reason, even though the experimental study on fish is considered technically invalid due to the exceptionally low recovery rate of 46.9%, while analytical validity guidelines do not accept values <70%, recalculating for this loss corrects the LC50 to the predicted value. The test can therefore be considered as a supporting study in this case.

Key value for chemical safety assessment

LC50 for freshwater fish:
71 mg/L

Additional information

A valid QSAR model and a reliability-3 study (Klimisch rating) on Zebra fish allowed to assess the aquatic toxicity of the registered substance.

The QSAR used is based on validated data for a training set of 32 esters 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 model provides 96h-LC50 predictions for fish from High Accuracy QSAR models which are based on ecotoxicologically validated studies and statistically validated regressions for a series of Modes of Action described within the QMRF. As such the results from these studies are considered accurate enough to replace an experimental study when the test substance falls within the appropriate applicability domain.

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.

The acute toxicity of the test item to Zebra fish (Brachydanio rerio) was assessed according to OECD Guideline 203, according to the Guidelines for the Testing of Chemicals, 203 Fish Acute toxicity test, China environmental Science Press (2004), and according to the guidelines for the testing of chemicals (HJ/T 153 -2004), China Environmental Science Press (2004). This reliability-3 study (Klimisch rating) from Guangdong Detection Center of Microbiology, 2012, is a supporting study.

The test item was tested at five nominal concentrations : 19.8 % LS (of the saturation solution), 29.6 % LS, 44.4 % LS, 66.7 % LS and 100 % LS. The five measured concentrations were : 5.206 mg/L, 8.142 mg/L, 13.15 mg/L, 21.54 mg/L and 35.06 mg/L.The test was semi-static and ran for 96 h. A blank control (test water without test substance) was run in parallel with the test concentrations. 7 fish were placed into each test vessel.

Analysis of the efficacy of the recovery of the sample (three replicates) revealed a procedural average recovery of 46.9 % (47.25 %, 45.00 %, 48.59 %). It was not indicated that results were corrected according to the level of recovery. Analysis of test media revealed that the test item concentrations were not maintained within 80 - 120 % of the nominal values.

Under the test conditions, the 96h-LC50 for the test item was 30.4 mg/L, the highest concentration causing 0 % mortality (LC0) was 5.206 mg/L and the lowest concentration causing 100 % mortality (LC100) was greater than 35.06 mg/L (calculated based on the geometric mean of actual concentration of 100 % LS group). These concentrations were not corrected according to the recovery level.

When the 96h-LC50 (30.4 mg/L) is multiplied by two (60.8 mg/L), the procedural average recovery being 46.9 %, the value that is obtained is closer to the 96h-LC50 value predicted with the valid QSAR model (71 mg/L).