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Toxicity to aquatic algae and cyanobacteria

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Reference
Endpoint:
toxicity to aquatic algae and cyanobacteria
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
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:
Data is from OECD QSAR toolbox version.3.3 and QMRF report has been attached.
Qualifier:
according to
Guideline:
OECD Guideline 201 (Alga, Growth Inhibition Test)
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3 with log kow as the primary discriptors.
GLP compliance:
no
Specific details on test material used for the study:
- Name of test material (as cited in study report): 4-Methylpiperazin-1-amine
- Molecular formula: C5H13N3
- Molecular weight: 115.179 g/mol
- Substance type: organic
- Physical state: Liquid
- Smiles notation: N1(CCN(CC1)C)N
- InChl: 1S/C5H13N3/c1-7-2-4-8(6)5-3-7/h2-6H2,1H3
Analytical monitoring:
no
Vehicle:
no
Test organisms (species):
Pseudokirchneriella subcapitata (previous names: Raphidocelis subcapitata, Selenastrum capricornutum)
Test type:
static
Water media type:
freshwater
Limit test:
no
Total exposure duration:
72 h
Key result
Duration:
72 h
Dose descriptor:
EC50
Effect conc.:
108.59 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
growth rate
Remarks on result:
other: NOT TOXIC

The prediction was based on dataset comprised from the following descriptors: EC50
Estimation method: Takes average value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" or "c" )  and "d" )  and ("e" and ( not "f") )  )  and "g" )  and ("h" and ( not "i") )  )  and "j" )  and "k" )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and "p" )  and "q" )  and "r" )  and ("s" and "t" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aliphatic Amines by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives by DNA binding by OASIS v.1.3 ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as SN1 AND SN1 >> Iminium Ion Formation AND SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines by DNA binding by OECD ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> beta-Lactams  by Protein binding by OASIS v1.3

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD ONLY

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Moderately reactive (GSH) OR Moderately reactive (GSH) >> 2-Vinyl carboxamides (MA) by Protein binding potency

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Class 5 (Not possible to classify according to these rules) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Very fast by Bioaccumulation - metabolism half-lives ONLY

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Barbital and ETU, PLTU-like derivatives (17a) OR Known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Alkali Earth OR Transition Metals by Groups of elements

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "q"

Similarity boundary:Target: CN1CCN(N)CC1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "r"

Similarity boundary:Target: CN1CCN(N)CC1
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.98

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.377

Conclusions:
Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the toxicity on algae was predicted for 4-methylpiperazin-1-amine (Cas no. 6928-85-4). Effect concentration i.e EC50 value was estimated to be 108.59 mg/l for Pseudokirchneriella subcapitata for 96 hrs duration.
Executive summary:

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the toxicity on algae was predicted for 4-methylpiperazin-1-amine (Cas no. 6928-85-4). Effect concentration i.e EC50 value was estimated to be 108.59 mg/l for Pseudokirchneriella subcapitata for 96 hrs duration. It was concluded that the 4-methylpiperazin-1-amine (Cas no. 6928-85-4) was likely to be not-toxic to aquatic algae, hence it can be considered to be “not classified” as per the CLP classification criteria for aquatic environment.

Description of key information

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the toxicity on algae was predicted for 4-methylpiperazin-1-amine (Cas no. 6928-85-4). Effect concentration i.e EC50 value was estimated to be 108.59 mg/l for Pseudokirchneriella subcapitata for 96 hrs duration. It was concluded that the 4-methylpiperazin-1-amine (Cas no. 6928-85-4) was likely to be not-toxic to aquatic algae, hence it can be considered to be “not classified” as per the CLP classification criteria for aquatic environment.

Key value for chemical safety assessment

EC50 for freshwater algae:
108.59 mg/L

Additional information

Four studies including predicted data from validated tools and experimental data from peer reviewed journal for toxicity to aquatic algae endpoint of test chemical 4-methylpiperazin-1-amine (Cas no. 6928-85-4) with relevant read across which is close to target using log Kow as primary descriptor were

summarised as follows:

 

Using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the six closest read across substances, the toxicity on algae was predicted for 4-methylpiperazin-1-amine (Cas no. 6928-85-4). Effect concentration i.e EC50 value was estimated to be 108.59 mg/l for Pseudokirchneriella subcapitata for 96 hrs duration. It was concluded that the 4-methylpiperazin-1-amine (Cas no. 6928-85-4) was likely to be not-toxic to aquatic algae, hence it can be considered to benot classifiedas per the CLP classification criteria for aquatic environment.

 

Similar prediction by EPI suite, ECOSAR version 1.1, On the basis of EPI suite, ECOSAR version 1.1, the EC50 value for toxicity to aquatic algae was predicted to be 12583.529 mg/l for 4-methylpiperazin-1-amine in 96 hrs. Based on the EC50 value, it can be concluded that the substance 4-methylpiperazin-1-amine was likely to be not-toxic to aquatic algae, hence it can be considered to benot classifiedas per the CLP classification criteria for aquatic environment.

 

Above predicted results for target is assisted by experimental data of read across chemicalMetformin(Cas no. 657-24-9) from Toxicology Letters 2003,indicates that the Effective concentration to 50% of Desmodesmus subspicatus at which decrease in population growth rate was measured is 320 mg/L. It can be concluded that the Metformin is not toxic to the aquatic environment.

Another experimental data of read acrossN,N-dimethylformamide (Cas no. 68-12-2) from Bulletin of Environmental Contamination and Toxicology 1983 indicates that NOEC value for Selenastrum capricornutum in 14 days is 470 mg/l. It can be concluded that the N,N-dimethylformamide is not toxic.

Thus based on the effect concentrations which is in the range 108.59 mg/l to 12583.529 mg/Lgive the conclusion that test substanceSulphoacetic acid(Cas no.123-43-1) was likely to be non-toxic to aquatic algae at environmentally relevant concentrations and can be considered to be not classified as per the CLP classification criteria.