N,N'-[bicyclo[2.2.1]heptane-2,6-diylbis(methylene)]bis(2-cyanoacetamide)

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

25th March 2020

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. SOFTWARE

US EPA EPISUITE

2. MODEL (incl. version number)
v1.11 ECOSAR

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL

SMILES : C1(CC2C(CC1C2)CNC(=O)(CC(#N)))CNC(=O)(CC(#N))
CHEM : NBDA-Cyanoacetamide
CAS Num:
ChemID1:
MOL FOR: C15 H20 N4 O2
MOL WT : 288.35

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint:
Acute Aquatic Toxicity to Daphnia

- Unambiguous algorithm:
ESTIMATED TOXICITY:
The daphnid 48-h LC50 values used to develop this SAR were measured, and the octanol water
partition coefficients (Kow) were calculated using the computer program, KOWWIN (Version
1.67). The SAR equation used to estimate toxicity is:
Log 48-h LC50 (mmol/L) = -0.9152 (log Kow) + 1.3475
The LC50 is in millimoles per liter (mM/L); N = 12 + 12; and the Coefficient of Determination (R2)
= 0.7924. To convert the LC50 from mM/L to mg/L, multiply by the molecular weight of the
compound.
Maximum Kow: 5.0
Maximum MW: 1000

Graph presenting data correlation and training set (SAR for amides, Daphnia 48-h LC50) is available in the ECOSAR, EPISUITE v1.11 handbook

- Defined domain of applicability:
In the development of the ECOSAR equations for neutral organics and classes with excess toxicity, the training sets generally include chemicals with log Kow values in the range of -3 to 8 and molecular weights less than 1000. However, the domain of the model is considered to be larger than the descriptor range of the training set of chemicals. It has been determined through empirical data that for acute toxicity endpoints, chemicals with a log Kow value >5.0 are generally expected to have no effects at saturation. For chronic effects, chemicals with a log Kow value >8.0 are expected no effects at saturation. Although the individual equations may not have been not built using chemicals with log Kow values greater than 5.0 and 8.0 respectively, the model can still make accurate qualitative determination of potential toxicity under environmental conditions for chemicals outside the log Kow descriptor domain. For classes where studies were available that exceed the log Kow limits, the data have been provided in the QSAR Equation Documents under the section labeled “SAR Data not included in Regression Equation” of the ECOSAR MethodologyDocumentV111.

- Mechanistic interpretation:
Selection of the appropriate QSAR within ECOSAR is based on a variety of information depending on the chemical class. This includes factors like the chemical structure, chemical class, log Kow, molecular weight, physical state, water solubility, number of carbons or ethoxylates (or both), and percent amine nitrogen or number of cationic charges (or both) per 1000 molecular weight. The most important factor for selecting an appropriate QSAR is the chemical class, since the QSARs in ECOSAR are class-specific.
To estimate the toxicity to aquatic organisms of neutral organics and organic classes with excess toxicity, the log Kow and molecular weight are required. In general, when the log Kow is less than or equal to 5.0 for fish and daphnid, or 6.4 for green algae, ECOSAR provides reliable quantitative (numeric) toxicity estimates for acute effects. If the log Kow exceeds those general limits, empirical data indicate that the decreased solubility of these lipophilic chemicals results in “no effects at saturation” during a 48-hour to 96-hour test.

5. APPLICABILITY DOMAIN
In the development of the ECOSAR equations for neutral organics and classes with excess toxicity, the training sets generally include chemicals with log Kow values in the range of -3 to 8 and molecular weights less than 1000. However, the domain of the model is considered to be larger than the descriptor range of the training set of chemicals. It has been determined through empirical data that for acute toxicity endpoints, chemicals with a log Kow value >5.0 are generally expected to have no effects at saturation. Although the individual equations may not have been not built using chemicals with log Kow values greater than 5.0 and 8.0 respectively, the model can still make accurate qualitative determination of potential toxicity under environmental conditions for chemicals outside the log Kow descriptor domain. Further information can be found in the ECOSAR EPISUITE Methodoloy Document, the data have been provided in the QSAR Equation Documents under the section labeled “SAR Data not included in Regression Equation”. NOTE: Log Kow cut offs can be class specific where data indicated a departure from this general trend of 5.0 for acute effects, and 8.0 for chronic effects.

For this substance Log Kow values were calculated using the EPISUITE tool, therefore limiting the robustness of the aquatics predictions.

Qualifier:

no guideline available

Principles of method if other than guideline:

Method follows European Chemicals Agency Practical Guide on How to Use and Report QSARs Version 3.1
Estimated data are obtained from a reliable (Q)SAR program developed and validated by the United States Environmental Protection Agency (U.S. EPA). This program is included in the OECD (Q)SAR Toolbox for use in filling REACH datagaps

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

376.32 mg/L

Remarks on result:

other: ECOSAR V1.11 prediction.

Validity criteria fulfilled:

not applicable

Conclusions:

The LC50 48h acute toxicity to Daphnia was predicted as 376.32 mg/L.

Description of key information

The LC50 48h acute toxicity to Daphnia was predicted as 376.32 mg/L.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

376.32 mg/L