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Ecotoxicological information

Long-term toxicity to fish

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Administrative data

Endpoint:
long-term toxicity to fish
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2013

Materials and methods

Test guideline
Guideline:
other: QSAR model for Fish, early-life stage toxicity test, model version: 08.12.2010, to predict ecotoxic long-term effects to fish (egg/sac fry, growth inhibition of juvenile fish, early life stage, full life cycle)
Principles of method if other than guideline:
QSAR model for Fish, early-life stage toxicity test, model version: 08.12.2010, to predict ecotoxic long-term effects to fish (egg/sac fry, growth inhibition of juvenile fish, early life stage, full life cycle)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
3D Mol files used for prediction, with descriptor values of 1,4-diethylbenzene:

descriptor name
FHACA Fractional HACA (HACA/TMSA) (AM1): 0
Polarity parameter (AM1) / square distance: 0.03
The octanol/water partition coefficient (calc.): 3.24

SMILES: CCC1=CC=C(CC)C=C1, not used for prediction
InChI: InChI=1S/C10H14/c1-3-9-5-7-10(4-2)8-6-9/h5-8H,3-4H2,1-2H3, not used for prediction

Results and discussion

Effect concentrationsopen allclose all
Dose descriptor:
NOEC
Effect conc.:
419 µg/L
Remarks on result:
other: predicted value
Dose descriptor:
NOEC
Effect conc.:
0.419 mg/L
Remarks on result:
other: predicted value

Any other information on results incl. tables

 Applicability domain (OECD principle 3)

a.      Domains: 

                 i.                  descriptor domain: All descriptor values for 1,4-diethylbenzene fall in the applicability domain (training set values ±30%). 

                ii.              structural fragment domain: 1,4-diethylbenzene is structurally similar to the training set compounds, the training set contains compounds featuring benzene rings with short alkyl substitutions. The training set contains compounds of similar size tothe studied molecule.

                  iii.              mechanism domain: 1,4-diethylbenzene is considered to be in the same mechanistic domain as the molecules in the training set as it is structurally similar to the model compounds.

                   iv.              metabolic domain, if relevant: 1,4 -diethylbenzen is considered to be in the same metabolic domain as the molecules in the training set of the model due to structural similarity.

b.      Structural analogues: 

CAS

structure

smiles

source

log(NOEC)

exp.

pred.

108-88-3

Cc1ccccc1

training

1.64

1.58

106-43-4

Cc1ccc(cc1)Cl

training

1.18

0.825

106-46-7

Clc1ccc(cc1)Cl

training

0.65

0.939

c.     Considerations on structural analogues: 

The experimental fish early-life stage toxicity values for structurally similar compounds are all found close in the same region as the prediction – there is an obvious trend for higher toxic potency for compounds with more hydrophobic groups. The structural analogues are functionally relatively similar to the studied compound. The descriptor values of the analogues are close to those of the studied compound. The analogues are considered to be within the same mechanistic domain. All the analogues are correctly estimated within the model.

Applicant's summary and conclusion

Validity criteria fulfilled:
yes
Conclusions:
According to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS), since the compound is not readily (bio)degradable, the following classification is available:

Study Category Chronic 1 Category Chronic 2
NOEC (fish) (mg/L) NOEC ≤ 0.1 0.1 ≤ NOEC ≤ 1.0

The predicted value for 1,4-diethylbenzene falls under the “Category Chronic 2” classification.

The corresponding EU grading reads: Harmful to aquatic organisms & May cause long-term adverse effects in the aquatic environment.


Executive summary:

 The chemical and biological mechanisms according to the model underpinning the predicted result (OECD principle 5). 

The main part of the variance of the endpoint values is covered by the (calculated) octanol/water partition coefficient indicating strong dependence on the hydrophobicity of the compounds. The negative coefficient indicates that compounds of higher logKow values (more hydrophobic) show increased toxicity. The hydrogen bond acceptor and dipolarity properties of molecules leading to specific interactions are described by the other two descriptors (FHACA Fractional HACA (HACA/TMSA) (AM1), Polarity parameter (AM1)/ square distance) and appear as minor correction terms.

The present structure contains only hydrophobic structural features but no long alkyl chains. There are no polar groups to increase water solubility. Overall the size, the structural features and the hydrophobic nature of the compound support the predicted toxic potency.