Registration Dossier

Administrative data

Endpoint:
short-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
01/03/2018-02/03/2018
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
Justification for type of information:
1. SOFTWARE

2. MODEL (incl. version number)
: iSafeRat® High-Accuracy-Quantitative Structure-Activity Relationship (HA-QSAR) based on a holistic approach for predicting physicochemical and ecotoxicological endpoints: Short-term toxicity to fish (lethality) ; version iSafeRat® holistic HA-QSAR v1.8

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
: C([C@H]([C@H](CO)O)O)O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Reference to QMRF: KTS/QMRF/HOL/08
QMRF Identifiers: Q19-46-51-448
QMRF Identifier (title): iSafeRat® HA-QSAR based on a holistic approach for predicting physicochemical and ecotoxicological endpoints.
- Defined endpoint:
Short-term toxicity to fish (lethality) ; log LC50 (mol/L)
- Unambiguous algorithm:
- Defined domain of applicability:
- Appropriate measures of goodness-of-fit and robustness and predictivity:
- Mechanistic interpretation:

5. APPLICABILITY DOMAIN
- Descriptor domain:
The water solubility value given as the input to the Ecotox module of the iSafeRat® Holistic HA-QSAR does not fall within the descriptor domain of the model between a log water solubility (in log (mol/L)) of - 4.63 to 0.87. Therefore, the prediction is considered as an extrapolation.
- Structural fragment domains: All chemical groups within the molecular structure are taken into account by the model.
- Mechanistic domains:
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)

(2S,3R)-BUTANE-1,2,3,4-TETROL as a polyol is expected to exert a MechoA 1.1 and can be taken into account by the model. The MechoA of molecules is predicted directly from the structure.

- Other considerations (as appropriate):
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 67 substances with the same MechoA as the test item.

(2S,3R)-BUTANE-1,2,3,4-TETROL falls within the applicability domain of the model except for the descriptor domain. The predicted toxicity (96h-LC50) to fish is considered as an extrapolation. Providing the high solubility of the test item in the water, no toxicity is expected below the threshold of 1000 mg/L.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: REACH Guidans on QSARs R.6
Version / remarks:
QSAR following OECD 203 EU C.1
Principles of method if other than guideline:
Not specified
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
C([C@H]([C@H](CO)O)O)O

Results and discussion

Effect concentrations
Key result
Duration:
96 h
Dose descriptor:
LC50
Effect conc.:
ca. 1 037 g/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
mortality
Remarks on result:
other: QSAR predicted value
Reported statistics and error estimates:
95% confidence interval (α = 0.05):
939 – 1146 g/L

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Conclusions:
The acute toxicity value anticipated during a 48-hour EC50 study on fish based on measured concentrations is : 1037 g test item/L