[No public or meaningful name is available]

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

supporting study

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:

ECOSAR Model
The structure-activity relationships (SARs) presented in this program are used to predict the aquatic toxicity of chemicals based on their similarity of structure to chemicals for which the aquatic toxicity has been previously measured. Most SAR calculations in the ECOSAR Class Program are based upon the octanol/water partition coefficient (Kow). Various surfactant SAR calculations are based upon the average length of carbon chains or the number of ethoxylate units.

The acute toxicity of a chemical to fish (both fresh and saltwater), water fleas (daphnids), and green algae has been the focus of the development of SARs, although for some chemical classes SARs are available for other effects (e.g, chronic toxicity and bioconcentration factor) and organisms (e.g., earthworms). SARs are developed for chemical classes based on measured test data that have been submitted by industry or they are developed by other sources for chemicals with similar structures, e.g., phenols. Using the measured aquatic toxicity values and estimated Kow values, regression equations can be developed for a class of chemicals. Toxicity values for new chemicals may then be calculated by inserting the estimated Kow into the regression equation and correcting the resultant value for the molecular weight of the compound.

There are currently 130 chemical classes programmed into ECOSAR. For those 130 classes, there are a total of 440 QSARs based on publicly available experimental data and confidential studies collected under the EPA New Chemicals Program. For each class, a standard EPA New Chemicals Program aquatic toxicity profile will be created using available QSARs and/or alternate SAR approaches and professional judgment. This standard profile typically contains 3 acute values, and 3 chronic values for fish, daphnid, and green algae. In an effort to complete a profile for each class, 173 endpoints have been estimated using alternative approaches such as acute-to-chronic ratios and substitute QSARs based on scientific judgment.

Toxicity is predicted at pH 7, TOC < 2%, moderate water hardness (150 mg/L CaCO3) and for 100% active ingredient.


1. SOFTWARE
ECOSAR Version 1.11

2. MODEL (incl. version number)
ECOSAR Version 1.11

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C[C@H](N)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C)N)C(O)=O)C(O)=O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint:
Decimal logarithm of the green algae 96h EC50 values in milimoles per liter (mmol/L)
- Unambiguous algorithm:
Log 96-h EC50 (mmol/L) = -0.6922 log Kow + 0.9253 (Neutral Organics)
Log 96-h EC50 (mmol/L) = -0.6214 (log Kow) – 0.7843 (Amides)
Log 96-h EC50 (mmol/L) = -0.7064 (log Kow) – 0.3109 (Aliphatic Amines)
The only descriptor used in the model is octanol-water partition coefficient, log Kow. Water solubility is relevant: if the EC50 exceeds the water solubility by 10x, no effects at saturation are predicted.
- Appropriate measures of goodness-of-fit and robustness and predictivity:
Neutral organics: N = 41 + 9 (number of compounds included + not included in regression equation), R² = 0.6782(coefficient of determination)
Amides: N = 8 + 4, R² = 0.2009
Aliphatic Amines: N = 35 + 11, R² = 0.7788
- Mechanistic Interpretation:
For acute effects caused by neutral organics, the mechanistic interpretation is related to the partitioning of the substance from water into the lipid phase of the organism (log Kow as mechanistically justified descriptor). This relationship is extrapolated to other classes of substances and to long term effects. In those cases it is assumed that basically log Kow remains a toxicity trigger and other specific or non-specific effects are included in the QSAR equation, determining the slope and the intercept.

5. APPLICABILITY DOMAIN
- Descriptor domain:
In principle, each ECOSAR model is applicable for substances belonging to the respective chemical class. The class of the substance is recognized by the program itself, based on the molecular structure. If no special class can be assigned, it is assumed that the compound belongs to the “neutral organics” class. It is however possible that the compound contains structural groups not represented in the training set (or represented there in less instances), so that the toxicity can be additionally influenced. These points should be taken into account while assessing the compliance with the applicability domain of the model.
Additionally, the applicability domain is estimated with respect to log Kow and molecular weight. For neutral organics, these are:
Maximum log Kow: 6.4, maximum MW: 1000 (Neutral Organics, Amides, and Aliphatic Amines).

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Software tool(s) used including version: ECOSAR Version 1.11
- Model description and Justification of QSAR prediction: see field 'Justification for type of information'

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

207 000 mg/L

Remarks on result:

other: QSAR: resuls for ECOSAR class Aliphatic Amins - acid

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

39 557 mg/L

Remarks on result:

other: QSAR: result for ECOSAR class Amides - acid

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

325 000 mg/L

Remarks on result:

other: QSAR: result for ECOSAR class Neutral Organic

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

> 100 mg/L

Remarks on result:

other: summarising QSAR result

Conclusions:

The predicted EC50 for all relevant classes is significantly > 100 mg/l

Description of key information

ErC10/50 (72 h) > 100 mg/L (nominal, OECD 201)