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Short-term toxicity to aquatic invertebrates

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Reference
Endpoint:
short-term toxicity to aquatic invertebrates
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:
other: Predicted data
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:
not specified
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):
Daphnia magna
Test type:
static
Water media type:
freshwater
Limit test:
no
Total exposure duration:
48 h
Key result
Duration:
48 h
Dose descriptor:
EC50
Effect conc.:
163.39 mg/L
Nominal / measured:
estimated
Conc. based on:
test mat.
Basis for effect:
other: Intoxication
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 ("i" and ( not "j") )  )  and ("k" and "l" )  )

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 >> Azlactones and unsaturated lactone derivatives  OR Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Acylation >> Direct acylation involving a leaving group >> N-Acylated heteroaromatic amines  OR Acylation >> Direct acylation involving a leaving group >> N-Acylsulfonamides  OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis >> Dithiocarbamates OR Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Quinone type chemicals OR Michael Addition >> Quinone type chemicals >> Pyranones, Pyridones (and related nitrogen chemicals)  OR Schiff base formation OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives OR Schiff base formation >> Pyrazolones and Pyrazolidinones derivatives >> Pyrazolones and Pyrazolidinones  OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  OR SN2 >> Nucleophilic substitution on benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc carbon atom >> alpha-Activated benzyls  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SNVinyl OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom OR SNVinyl >> SNVinyl at a vinylic (sp2) carbon atom >> Vinyl type compounds with electron withdrawing groups  by Protein binding by OASIS v1.3

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as Reactive unspecified by Acute aquatic toxicity MOA by OASIS ONLY

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.64

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.678

Conclusions:
Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 4-methylpiperazin-1-amine (Cas no. 6928-85-4). Effect concentration i.e EC50 value was estimated to be 163.39 mg/l for Daphnia magna for 48 hrs duration.
Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 4-methylpiperazin-1-amine (Cas no. 6928-85-4). Effect concentration i.e EC50 value was estimated to be 163.39 mg/l for Daphnia magna for 48 hrs duration. It was concluded that the 4-methylpiperazin-1-amine (Cas no. 6928-85-4) was likely to be not-toxic to aquatic invertebrates, 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 five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 4-methylpiperazin-1-amine (Cas no. 6928-85-4). Effect concentration i.e EC50 value was estimated to be 163.39 mg/l for Daphnia magna for 48 hrs duration. It was concluded that the 4-methylpiperazin-1-amine (Cas no. 6928-85-4) was likely to be not-toxic to aquatic invertebrates, 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/LC50 for freshwater invertebrates:
163.39 mg/L

Additional information

Four studies including predicted data from validated tools and experimental data from peer reviewed journal for toxicity to aquatic invertebrate 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 five closest read across substances, the short term toxicity on aquatic invertebrates was predicted for 4-methylpiperazin-1-amine (Cas no. 6928-85-4). Effect concentration i.e EC50 value was estimated to be 163.39 mg/l for Daphnia magna for 48 hrs duration. It was concluded that the 4-methylpiperazin-1-amine (Cas no. 6928-85-4) was likely to be not-toxic to aquatic invertebrates, hence it can be considered to benot classifiedas per the CLP classification criteria for aquatic environment.

 

Similar prediction done by Using the EPI Suite ECOSAR version 1.11, the LC50 value for short term toxicity to aquatic invertebrate was predicted to be 406.90 mg/l for 4-methylpiperazin-1-amine in 48 hrs. Based on the LC50 value, it can be concluded that the substance 4-methylpiperazin-1-amine is not toxic.

 

Above predicted results for target is assisted by experimental data of read across chemicalN,N-dimethylformamide(Cas no. 68-12-2) from handbook,The Lethal concentration to 50% (LC50) of Crangon crangon is 100 mg/l at 48 h. On the basis of the value it can be concluded that the N,N-dimethylformamide is not toxic to the aquatic environment.

 

Another experimental data of read acrossN,N-dimethylformamide (Cas no. 68-12-2) from Archives of Environmental Contamination and Toxicology 1983 indicates that the lethal concentration LC50 for daphnia magna at 48 hrs is 12350 mg/l. It can be concluded that the N,N-dimethylformamide is not toxic to aquatic environment.

Thus based on the effect concentrations which is in the range100mg/l to12350give the conclusion that test substance 4-methylpiperazin-1-amine (Cas no. 6928-85-4) was likely to be non-toxic to aquatic invertebrate at environmentally relevant concentrations and can be considered to benot classifiedas per the CLP classification criteria.