Piperazine adipate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ames Test:

The prediction is done for piperazine adipate for S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 for genetic toxicity with and without metabolic activation is estimated to be negative. Based on this value it can be conclude that piperazine adipate is not toxic for genetic effects.

Chromosome aberration

The prediction is done for piperazine adipate for Chinese Hamster Lung for genetic toxicity without metabolic activation is estimated to be negative. Based on this value it can be conclude that piperazine adipate is not toxic for genetic effects.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

QSAR prediction is done using the QSAR toolbox version 3.0

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with

Metabolic activation system:

S9

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

((("a" and ("b" and ( not "c") ) ) and "d" ) and ("e" and "f" ) )

Domain logical expression index: "a"

Similarity boundary:Target: C(=O)(O)CCCCC(=O)O_C1CNCCN1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.1

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Acyl transfer via nucleophilic addition reaction OR Acylation >> Acyl transfer via nucleophilic addition reaction >> Haloalkenes with Electron-Withdrawing Groups OR Elimination (E2) OR Elimination (E2) >> E2 elimination reaction with epoxide formation OR Elimination (E2) >> E2 elimination reaction with epoxide formation >> Haloalcohols OR Michael addition OR Michael addition >> alpha, beta-unsaturated carabonyl compounds OR Michael addition >> alpha, beta-unsaturated carabonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR Michael addition >> alpha, beta-unsaturated carabonyl compounds >> Four- and Five-Membered Lactones OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinoneimine Derivatives OR Michael addition >> Quinone type compounds >> Quinones OR Nucleophilic addition OR Nucleophilic addition >> Nucleophilic addition reaction with cycloisomerization OR Nucleophilic addition >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Coumarins OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical decomposition OR Radical >> Radical decomposition >> Alkylnitrites OR Radical >> Radical mechanism by ROS formation OR Radical >> Radical mechanism by ROS formation >> Hydrazine Derivatives OR Radical >> Radical mechanism by ROS formation >> Nitro Compounds OR Radical >> Radical mechanism by ROS formation >> Nitroso compounds OR Radical >> Radical mechanism by ROS formation >> Organic Peroxy Compounds OR Radical >> Radical mechanism by ROS formation >> Quinones OR Radical >> Radical mechanism by ROS formation >> Specific Imine and Thione Derivatives OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Aromatic and Heterocyclic Primary Amines OR Radical >> ROS formation after GSH depletion >> Haloalcohols OR Radical >> ROS formation after GSH depletion >> Quinoneimine Derivatives OR Schiff base fomers OR Schiff base fomers >> Direct acting Schiff base formers OR Schiff base fomers >> Direct acting Schiff base formers >> Alkylnitrites OR Schiff base fomers >> Direct acting Schiff base formers >> Alpha, Beta-Unsaturated Aldehydes OR Schiff base fomers >> Direct acting Schiff base formers >> Dicarbonyl Compounds OR Schiff base fomers >> Direct acting Schiff base formers >> Specific Acetate Esters OR Schiff base fomers >> Multi-step Shiff base formation OR Schiff base fomers >> Multi-step Shiff base formation >> Haloalkanes Containing Electron-Withdrawing Groups OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Nitroso compounds OR SN1 >> Carbenium ion formation >> Specific Acetate Esters OR SN1 >> Glutathione-induced nitrenium ion formation OR SN1 >> Glutathione-induced nitrenium ion formation >> Nitroso compounds OR SN1 >> Nitrenium and/or Carbenium ion formation OR SN1 >> Nitrenium and/or Carbenium ion formation >> Urea Derivatives OR SN1 >> Nitrenium ion and/or Acyl ion formation OR SN1 >> Nitrenium ion and/or Acyl ion formation >> N-acyloxy-N-alkoxyamides OR SN1 >> Nitrenium ion formation OR SN1 >> Nitrenium ion formation >> Aromatic and Heterocyclic Primary Amines OR SN1 >> Nitrenium ion formation >> N-hydroxylamines OR SN1 >> Nitrenium ion formation >> Nitro Compounds OR SN1 >> Nitrosation OR SN1 >> Nitrosation >> Alkylnitrites OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation >> Nitroso compounds OR SN1 >> Non-enzymatic nitroso radical and/or nirtosonium cation formation >> Urea Derivatives OR SN2 OR SN2 >> Acylating agents OR SN2 >> Acylating agents >> Specific Acetate Esters OR SN2 >> Carbenium Ion Formation OR SN2 >> Carbenium Ion Formation >> Acyclic Triazenes OR SN2 >> Carbenium Ion Formation >> Diazoalkanes OR SN2 >> Diazonium ion formation OR SN2 >> Diazonium ion formation >> Specific Imine and Thione Derivatives OR SN2 >> Direct Acting Epoxides and Related OR SN2 >> Direct Acting Epoxides and Related >> Epoxides, Aziridines OR SN2 >> Direct Acting Epoxides and Related >> Nitrogen Mustards OR SN2 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> Epoxidation of Aliphatic Alkenes OR SN2 >> Epoxidation of Aliphatic Alkenes >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Epoxidation of Aliphatic Alkenes >> Polarized Haloalkene Derivatives OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Electron-Withdrawing Groups OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom OR SN2 >> P450-mediated epoxidation OR SN2 >> P450-mediated epoxidation >> Coumarins OR SN2 >> P450-mediated epoxidation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> P450-mediated epoxidation >> Polarized Haloalkene Derivatives OR SN2 >> P450-mediated epoxidation >> Quinoline Derivatives OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Ring opening SN2 reaction >> Haloisothiazolinones OR SN2 >> SN2 at an activated sp2 (aromatic) carbon atom OR SN2 >> SN2 at an activated sp2 (aromatic) carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at Nitrogen Atom OR SN2 >> SN2 at Nitrogen Atom >> N-acetoxyamines OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> SN2 at sp3-carbon atom >> Specific Acetate Esters OR SN2 >> SN2 at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> SN2 at sulfur atom OR SN2 >> SN2 at sulfur atom >> Sulfonyl Halides by DNA binding by OASIS v.1.1

Domain logical expression index: "d"

Similarity boundary:Target: C(=O)(O)CCCCC(=O)O_C1CNCCN1
Threshold=50%,
Dice(Atom pairs)

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.56

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.202

Conclusions:

Interpretation of results (migrated information):
negative

The prediction is done for piperazine adipate for S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 for genetic toxicity with metabolic activation is estimated to be negative. Based on this value it can be conclude that piperazine adipate is not toxic for genetic effects.

Executive summary:

The prediction is done for piperazine adipate for S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 for genetic toxicity with metabolic activation is estimated to be negative. Based on this value it can be conclude that piperazine adipate is not toxic for genetic effects.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Summary of weight of evidence – Genetic Toxicity

No of studies reviewed for Genetic toxicity from reliable sources having Klimish rating 2 and 4

The summary if the results are presented below

 

Sr. No	Endpoint name	Value	Test method	Species	Source
1	Genotoxicity	Negative	Ames test	S. typhimurium TA 1535, TA 1537, TA 98 and TA 100	Prediction report
2	Genotoxicity	Negative	Ames test	S. typhimurium TA 1535, TA 1537, TA 98 and TA 100	Prediction report
3	Genotoxicity	Negative	chromosome aberration	Chinese Hamstar Lung (chl)	Prediction report
4	Genotoxicity	Negative	Ames test	S. typhimurium	DEPA
5	Genotoxicity	Negative	chromosome aberration	Chinese hamster Ovary (CHO)	DEPA
6	Genotoxicity	Negative	HGPRT forward mutation assay	Chinese hamster Ovary (CHO)	DEPA
7	Genotoxicity	Negative	genome mutation	yrian hamster embryo cell	DEPA

 

Based on the above values it can be seen that the Genotoxicity values is negative based on different species and different method. Thus from above values it can be concluded that the piperazine adipate is not genetically toxic substance based on the classification criteria of CLP regulation.

Justification for selection of genetic toxicity endpoint

The prediction is done for piperazine adipate for S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 for genetic toxicity with metabolic activation is estimated to be negative. Based on this value it can be conclude that piperazine adipate is not toxic for genetic effects.