Piperazine adipate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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

Guideline:

other: OECD Guideline 401 (Acute Oral Toxicity);OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

QSAR prediction is done using the OECD QSAR Toolbox Version 3.0

GLP compliance:

not specified

Test type:

other: standard acute method;Similar to OECD TG 401;acute toxic class method

Species:

rat

Strain:

other: Sprague-Dawley;Wistar;no data

Sex:

male/female

Route of administration:

other: oral: gavage;oral: unspecified

Vehicle:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 782 mg/kg bw

Based on:

test mat.

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

(((((("a" and ("b" and ( not "c") ) ) and ("d" and ( not "e") ) ) and "f" ) and "g" ) and "h" ) and ("i" and "j" ) )

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 Protein binding by OASIS v1.1

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 >> Isocyanates and isothiocyanates OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Acid anhydrides OR Acylation >> Direct acylation involving a leaving group >> Acyl halide of carboxylic acids OR Acylation >> Direct acylation involving a leaving group >> N-acylamides OR Acylation >> Direct acylation involving a leaving group >> N-acylsulphonamides OR Acylation >> Direct acylation involving a leaving group >> Sulphonyl halides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated alkyl or aryl esters OR Acylation >> Ring opening acylation OR Acylation >> Ring opening acylation >> Active cyclic agents OR Ionic OR Ionic >> Electrostatic interaction of tetraalkylammonium ions with protein carboxylates OR Ionic >> Electrostatic interaction of tetraalkylammonium ions with protein carboxylates >> Tetraalkylammonium ions OR Michael addition OR Michael addition >> a,b-unsaturated carbonyl compounds OR Michael addition >> a,b-unsaturated carbonyl compounds >> a,b-unsatuarted aldehydes 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 >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes OR Michael addition >> Michael type addition on vinyl pirydines and activated ethenylarenes >> Vinyl pyridines OR Nucleophilic addition OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond OR Nucleophilic addition >> Addition to Carbon-hetero double/triple bond >> Ketones OR Radical OR Radical >> Free radical formation OR Radical >> Free radical formation >> Organic peroxy compounds OR Schiff base formation OR Schiff base formation >> Nucleophilic cycloaddition to diketones OR Schiff base formation >> Nucleophilic cycloaddition to diketones >> Diketones OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes 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 >> Activated alkyl esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-activated haloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> alpha-haloalkanes OR SN2 >> Nucleophilic substitution on benzylic carbon atom OR SN2 >> Nucleophilic substitution on benzylic carbon atom >> alpha-activated benzyls OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes OR SN2 >> Ring opening SN2 reaction >> Isothiazolones derivatives OR SNAr OR SNAr >> Nucleophilic aromatic substitution on activated halogens OR SNAr >> Nucleophilic aromatic substitution on activated halogens >> Activated haloarenes by Protein binding by OASIS v1.1

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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 >> Acetates OR SN2 OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-pyridines by Protein binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as High (Class III) AND Low (Class I) by Toxic hazard classification by Cramer (original)

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.612

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.379

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The lethal dose (LD50) of rat for 6 hours for piperazine adipate is estimated to be 3782 mg/kg bw. Based on this value it can be concluded that piperazine adipate is practically non toxic substance via oral route.

Executive summary:

The lethal dose (LD50) of rat for 6 hours for piperazine adipate is estimated to be 3782 mg/kg bw. Based on this value it can be concluded that piperazine adipate is practically non toxic substance via oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 782 mg/kg bw

Quality of whole database:

K2 data predicted from QSAR toolbox version 3.0

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Guideline:

other: Not Applicable

Principles of method if other than guideline:

QSAR prediction is done using the OECD QSAR Toolbox Version 3.0

GLP compliance:

not specified

Test type:

other: Acute Rodent Inhalation Toxicity Test

Species:

rat

Strain:

Long-Evans

Sex:

male

Route of administration:

inhalation

Type of inhalation exposure:

other: Inhalation: Vapor

Vehicle:

not specified

Duration of exposure:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

880.496 ppm

Based on:

test mat.

Exp. duration:

8 h

The prediction was based on dataset comprised from the following descriptors: LC50
Estimation method: Takes average value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

("a" and ("b" and "c" ) )

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"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.856

Domain logical expression index: "c"

Parametric boundary:The target chemical should have a value of log Kow which is <= 1.62

Interpretation of results:

other: Other: Slightly toxic or Practically nontoxic

Conclusions:

The lethal concentration (LC50) of rat via inhalation: vapor route for piperazine adipate is estimated to be 880.49 mg/l. Based on this value it can be concluded that piperazine adipate is practically non toxic substance via inhalation route.

Executive summary:

The lethal concentration (LC50) of rat via inhalation: vapor route for piperazine adipate is estimated to be 880.49 mg/l. Based on this value it can be concluded that piperazine adipate is practically non toxic substance via inhalation route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Quality of whole database:

K2 data predicted from QSAR toolbox version 3.0

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Summary of weight of evidence - Acute toxicity: oral

No of studies reviewed for Acute toxicity: oral from reliable sources having Klimish rating 2 and 4

The summary if the results are presented below

 

Sr. No	Endpoint name	Value	Units	Species	Source
1	LD50	3782	mg/kg bw	Rat	Prediction report
2	LD50	4773.39	mg/kg bw	Mouse	Prediction report
3	LD50	8000	mg/kg bw	Rat	RTECS
4	LD50	7900	mg/kg bw	Rat	RTECS
5	LD50	7700	mg/kg bw	Mouse	SciFinder

 

Based on the above values it can be seen that the lethal dose (LD50) values varies between 3782 to 8000 mg/kg bw. From above values it can be concluded that the piperazine adipate is not toxic substance via oral route based on the classification criteria of CLP regulation.

Justification for selection of acute toxicity – oral endpoint

The lethal dose (LD50) of rat for 6 hours for piperazine adipate is estimated to be 3782 mg/kg bw. Based on this value it can be concluded that piperazine adipate is practically non toxic substance via oral route.

Justification for selection of acute toxicity – inhalation endpoint

The lethal concentration (LC50) of rat via inhalation: vapor route for piperazine adipate is estimated to be 880.49 mg/l. Based on this value it can be concluded that piperazine adipate is practically non toxic substance via inhalation route.

Justification for selection of acute toxicity – dermal endpoint

This end point was considered for waiver since direct and indirect exposure of the soil compartment with piperazine adipate is highly unlikely considering that the chemical is used as a drug and most likly route of exposure is only through oral route.