Registration Dossier

Ecotoxicological information

Short-term toxicity to fish

Currently viewing:

Administrative data

Link to relevant study record(s)

Referenceopen allclose all

Endpoint:
short-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
January 2021
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:
1. SOFTWARE : OECD QSAR Toolbox v4.4

2. MODEL: short-term 96h LC50 fish toxicity in pimephales promelas

3. SMILES USED AS INPUT FOR THE MODEL : FC(F)(Cl)Cl

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
see attached QTRF
- Defined endpoint: mortality
- Unambiguous algorithm: LC50 = 1,54 (±0,417) + 0,798 (±0,119) * log Kow, log(1/mol/L)
- Defined domain of applicability: log Kow: from 1,34 to 4,98
- Appropriate measures of goodness-of-fit and robustness and predictivity: R2 = 0,825; coefficient of determination
- Mechanistic interpretation: non-polar narcosis

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
- Descriptor domain: log Kow: from 1.34 to 4.98. The substance LogKow is 2.16 (exp) or 1.82 (est.)
- Structural domain: no closely-related structures present in the training set, no fluorinated compounds but some halogenated chemicals (common chemical elements present in all analogues).
- Mechanistic domain: grouping based on mode of action
- Similarity with analogues in the training set: grouping based on mode of action (non-polar narcosis)

6. ADEQUACY OF THE RESULT
the molecule falls within the applicability domain of the regression equation. The result is used in a weight of evidence for hazard assessment and classification.
Guideline:
other: REACH Guidance on QSARs R.6
Specific details on test material used for the study:
SMILES: FC(F)(Cl)Cl
Duration:
96 h
Dose descriptor:
LC50
Remarks:
Pimephales promelas
Effect conc.:
122 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
mortality (fish)
Remarks on result:
other: QSAR predicted value.
Details on results:
Range of predicted value: 122 mg/l (95% confidence interval: 18.9 to 786 mg/l)
r2: 0.825
Conclusions:
The acute fish LC50 (96h) was estimated using a QSAR model developed in the OECD QSAR toolbox.
Fish 96-hr LC50 = 122 mg/l for mortality endpoint in Pimephales promelas.
Endpoint:
short-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
January 2021
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:
QSAR Prediction
1. SOFTWARE : ECOSAR v2.00

2. MODEL: short-term fish toxicity for neutral organics (2012)
Log LC50 (mmol/L) = -0.8981 (log Kow) + 1.7108 , r2 = 0.878

3. SMILES USED AS INPUT FOR THE MODEL : FC(F)(Cl)Cl

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
see attached documents

5. APPLICABILITY DOMAIN
- Descriptor domain: Maximum LogKow: 5.0, maximum MW: 1000
see attached documents

6. ADEQUACY OF THE RESULT
The molecule falls within the applicability domains.
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Software tool(s) used including version: ECOSAR v2.0
- Model(s) used: prediction of potential short-term effects using ECOSAR v2.00 for estimation of aquatic toxicity of chemicals. (2012 updated training set)
- Model description: see field ''Attached justification'
- Justification of QSAR prediction: see field 'Attached justification'
GLP compliance:
no
Specific details on test material used for the study:
SMILES USED AS INPUT FOR THE MODEL: FC(F)(Cl)Cl
Water solubility: 280 mg/l
Duration:
96 h
Dose descriptor:
LC50
Remarks:
freshwater
Effect conc.:
145 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
mortality (fish)
Remarks on result:
other: QSAR predicted value
Remarks:
prediction using the default estimated LogKow
Duration:
96 h
Dose descriptor:
LC50
Remarks:
freshwater
Effect conc.:
71.35 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
mortality (fish)
Remarks on result:
other: QSAR predicted value
Remarks:
pediction using the experimental LogKow
Duration:
96 h
Dose descriptor:
LC50
Remarks:
saltwater fish
Effect conc.:
182.93 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
mortality (fish)
Remarks on result:
other: QSAR prediction
Remarks:
predicted value using estimated LogKow
Duration:
96 h
Dose descriptor:
LC50
Remarks:
saltwater fish
Effect conc.:
89.91 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
mortality (fish)
Remarks on result:
other: QSAR prediction
Remarks:
prediction using the expermiental LogKow
Details on results:
Results estimated by ECOSAR v2.00 for estimation of aquatic toxicity of chemicals. Refer to attached QPRF for details on the associated domains.
Validity criteria fulfilled:
yes
Remarks:
Substance within the applicability domain of the model
Conclusions:
Assessment of the short-term toxicity to fish was conducted using ECOSAR v2.0.
The 96-hr LC50 was determined to be 145 mg/l using the estimated LogKow of 1.82 (as calculated by KOWWIN). For saltwater species: 182.93 mg/l
The 96-hr LC50 was determined to be 71.35 mg/l using the measured LogKow of 2.16. For saltwater species: 89.91 mg/l

On the basis of this, it is proposed that the substance could be potentially hazardous to fish.
Endpoint:
short-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
January 2021
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Remarks:
The structure was out of Applicability Domain of most of the individual models
Justification for type of information:
1. SOFTWARE: ISIDA Predictor developed by Laboratoire De Chemoinformatique UMR 7140 CNRS, University of Strasbourg, Strasbourg, FR, 2019. (http://infochim.u-strasbg.fr/)

2. MODEL: ISIDA Consensus – Fish short-term toxicity (LC50) regression model (version October 2020)

3. SMILES USED AS INPUT FOR THE MODEL : FC(F)(Cl)Cl

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: mortality
- Details in attached QMRF

5. APPLICABILITY DOMAIN
- Details in attached QMRF

6. ADEQUACY OF THE RESULT
The prediction for this endpoint was considered of low reliability because the structure falls into the applicability domain of only 2/15 models.
Guideline:
other: REACH Guidance on QSARs R.6
Principles of method if other than guideline:
- Parameters : predicted mortality
- Software tool(s): ISIDA Predictor (version October 2020)
- Model(s) used: ISIDA Consensus – Fish short-term toxicity (LC50) regression model
- Model description: see QMRF in field 'Attached justification'
- Justification of QSAR prediction: see QPRF in field 'Attached justification'
GLP compliance:
no
Specific details on test material used for the study:
SMILES USED AS INPUT FOR THE MODEL: FC(F)(Cl)Cl
Duration:
96 h
Dose descriptor:
LC50
Effect conc.:
107.269 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
mortality (fish)
Remarks on result:
other: QSAR predicted value.
Remarks:
prediction considered of low reliability, as the structure was out of the AD of most models
Details on results:
The prediction was considered of low reliability because the structure falls into the applicability domain of only 2 out of 15 individual models, while the acceptability criteria for the consensus model would require at least 4/15 (>25%).
Conclusions:
The acute fish LC50 (96h) was estimated using a validated QSAR consensus model.
Fish 96-hr LC50 = 107.269 mg/l (with sd: 2.24). However the prediction was considered of low reliability because the structure is inside the applicability domain of only 2/15 individual models, while the acceptability criteria for the model would require at least 4/15.
On the basis of this, no conclusion can be made.

Description of key information

Assessment of acute toxicity to fish by weight of evidence based on several validated QSAR models. Range of predicted values:

96h LC50: 71 - 145 mg/l for freshwater species

96h LC50: 90 - 183 mg/l for saltwater species.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish
Dose descriptor:
LC50
Effect concentration:
>= 71 mg/L

Marine water fish

Marine water fish
Dose descriptor:
LC50
Effect concentration:
>= 90 mg/L

Additional information

The substance is listed in the Regulation (EC) No 2037/2000 of the European Parliament and of the Council of 29 June 2000 on substances that deplete the ozone layer lists within ANNEX I states that the substance is listed as a Group 1 substance. The substance is used as a processing agent under a derogation in accordance with Regulation (EC) No 1005/2009 of the European Parliament and of the Council of 16 September 2009 on substances that deplete the ozone layer. Fugitive emissions are controlled and there are no direct releases to the aquatic environment during industrial use.

Use of valid QSAR models was therefore considered appropriate for assessment of the toxicity to aquatic organisms. The lowest value obtained was a 96-hr LC50 of 71 mg/l for freshwater. Based on this result the substance could be potentially hazardous to fish.