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Ecotoxicological information

Short-term toxicity to aquatic invertebrates

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Administrative data

Endpoint:
short-term toxicity to aquatic invertebrates
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Study period:
2018-04-11
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 limited documentation / justification
Justification for type of information:
1. SOFTWARE
ECOlogical Structure Activity Relationship (ECOSAR) software v2.0

2. MODEL (incl. version number)
ECOSAR v2.0, October 2017

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Pentamer 6: O=C(C(CC1=O)NNC(C2=CC=CC(NC(C(N3C4=CC=C(CC5=CC=C(N6C(C(CC6=O)NC7=CC(C(NN)=O)=CC=C7)=O)C=C5)C=C4)=O)CC3=O)=C2)=O)N1C8=CC=C(CC9=CC=C(N%10C(C(CC%10=O)NNC(C%11=CC=CC(N)=C%11)=O)=O)C=C9)C=C8
Pentamer 5: O=C(C(CC1=O)NC2=CC(C(NNC(C(N3C4=CC=C(CC5=CC=C(N6C(C(CC6=O)NNC(C7=CC=CC(N)=C7)=O)=O)C=C5)C=C4)=O)CC3=O)=O)=CC=C2)N1C8=CC=C(CC9=CC=C(N%10C(C(CC%10=O)NNC(C%11=CC=CC(N)=C%11)=O)=O)C=C9)C=C8
Pentamer 4: O=C(C(CC1(=O))Nc2cc(C(=O)(NNC(C(=O)(N3c4ccc(Cc5ccc(N6C(=O)(C(CC6(=O))Nc7cc(C(=O)(NN))ccc7))cc5)cc4))CC3(=O)))ccc2)N1c8ccc(Cc9ccc(N%10C(=O)(C(CC(=O)%10)Nc%11cc(C(=O)(NN))ccc%11))cc9)cc8

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint:
Aquatic toxicity

- Unambiguous algorithm:
The QSARs in ECOSAR for both neutral organics and classes with excess toxicity are based on a linear mathematical relationship between the predicted log Kow values and the corresponding log of the measured toxicity values (mmol/L) for a suite of training set chemicals within each class of interest.

- Defined domain of applicability:
Currently there is no universally accepted definition of model domain. However, it should be considered that the estimates may be less accurate for compounds outside the molecular weight range of the training set compounds, and/or that have strongly differing log Kow as compared to training set compounds.

- Appropriate measures of goodness-of-fit and robustness and predictivity:
In its most simple design, an external evaluation uses chemicals not employed in the development of the model and takes the form of a direct comparison between the experimental and estimated values for the chemicals. When the predicted endpoint is quantitative (provides a numeric value), a regression analysis is performed comparing the experimental and estimated data to ascertain the coefficient of determination (r²) for the model. This coefficient of determination is used as a surrogate measure for the predictivity. The higher the r² value, the greater the correlation between experimental and estimated values, the better the predictive accuracy of the model.


5. APPLICABILITY DOMAIN

- Descriptor domain:
Water solubility, log Kow, molecular weight

- Structural and mechanistic domains:
The underlying predictive methodology is described in the reference listed below:
Meylan, WM; Howard, P. (1995) Atom/Fragment Contribution Method for Estimating Octanol-Water Partition Coefficients. J Pharm Sci 84: 83-92.

- Similarity with analogues in the training set:
The HELP menu in the ECOSAR Class Program contains QSAR Equation Documents for all QSARs within each chemical class to provide transparency in the QSAR methods and supporting measured data. However, since the structure contains groups with exceeding toxicity, i.e. other than narcosis, the estimated effect values for these moieties are also documented within the results section.

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Software tool(s) used including version: The Estimation Programs Interface (EPI) Suite™ v4.1 contains the ECOlogical Structure Activity Relationship (ECOSAR) software
- Model(s) used: ECOSAR v2.0
- Model description: see field 'Attached justification'
- Justification of QSAR prediction: see field 'Attached justification'
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Synthetic resin, a reaction product of 4,4'-bis(N-maleimido)diphenylmethane with 3-aminobenzoic acid hydrazide
EC Number:
619-370-5
Cas Number:
98725-11-2
Molecular formula:
Not applicable (UVCB substance)
IUPAC Name:
Synthetic resin, a reaction product of 4,4'-bis(N-maleimido)diphenylmethane with 3-aminobenzoic acid hydrazide

Results and discussion

Effect concentrationsopen allclose all
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
146.23 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for anilines (unhindered) class/Pentamer 5
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
112.17 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for hydrazine class/Pentamer5
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
11 714.67 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for imde class/Pentamer5
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
1 166 091.88 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for amide class/Pentamer5
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
294 516.24 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
averaged value for all classes/pentamer 5
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
110.03 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for anilines (unhindered) class/Pentamer6
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
84.52 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for hydrazine class/Pentamer6
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
6 492.09 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for imide class/Pentamer6
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
456 478.56 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for amide class/Pentamer6
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
115 791.3 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
averaged value for all classes/pentamer 6
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
63.68 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for hydrazine class/Pentamer
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
3 597.82 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for imide class/Pentamer
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
178 693.08 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
value for amide class/Pentamer
Key result
Duration:
48 h
Dose descriptor:
LC50
Effect conc.:
45 588.65 mg/L
Basis for effect:
mobility
Remarks on result:
other: QSAR prediction ECOSAR 2.0
Remarks:
averaged value for all classes/pentamer

Any other information on results incl. tables

Chemical may not be soluble enough to measure this predicted effect. If the effect level exceeds the water solubility by 10X, typically no effects at saturation (NES) are reported.

Applicant's summary and conclusion

Validity criteria fulfilled:
not applicable
Conclusions:
In the present QSAR prediction conducted with the EPISuite™; ECOSAR v2.0 software. The program detected functional groups present in the molecule which are considered to exhibit a more specific mode of toxicity, namely, anilines (unhindered), hydrazines, imides and amides. In consideration of the results of all chemical classes, four LC50 values are estimated. Most LC50 values predicted for Compimide 183 (Pentamer) are above the 100 mg/L limit concentration. Compimide 183 exhibits a low to moderate water solubility, the prediction reveales values which are exceeding the water solubility 10-fold. Thus, especially for the pentamer from Compimide 183 no effects at saturation are expected. Furthermore, the prediction obtained values from four different structure types, i.e. anilines (unhindered), hydrazines, imides and amides and the values for baseline toxicity. The occurrence of fragments other than the neutral organic SAR indicates effects that are mediated by other mechanisms than narcosis, thus, as a worst case the final prediction value is the lowest estimated value of these toxicity classes for the pentamers occurring in Compimide 183 (LC50 = 63.68 mg/L). Since the fragments found in Compimide 183 fall within the applicability domain of the used model and the predicted values are higher than the water solubility, no toxic effects are expected to occur up to saturation limits.