Piperazine adipate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

toxicity to reproduction

Remarks:

other: screening;repeated dose and reproductive/developmental toxicity screening test;combined repeated dose and reproduction / developmental screening;Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test

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: OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test);OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

QSAR prediction is done using the QSAR toolbox version 3.0

GLP compliance:

not specified

Species:

rat

Strain:

other: Sprague-Dawley;Slc:SD;Crj: CD(SD) IGS

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Frequency of treatment:

daily for 14 days prior to mating

Remarks:

Doses / Concentrations:
100, 300, and 1,000 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

12

Dose descriptor:

NOAEL

Effect level:

695.133 mg/kg bw/day

Based on:

other: not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: Generation: P;F1 (migrated information)

Critical effects observed:

not specified

Organ:

not specified

Dose descriptor:

other: not specified

Generation:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Critical effects observed:

not specified

System:

other: not specified

Organ:

not specified

Reproductive effects observed:

not specified

Treatment related:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
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 ( not "i") ) ) and ("j" and "k" ) )

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 Non binder, non cyclic structure AND Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

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 Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR SN2 OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Thiols 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"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Phthalates by rtER Expert System ver.1 - USEPA

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.801

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.364

Conclusions:

Based on the prediction done for piperazine adipate for two generation reproduction toxicity on rats, the esstimiated No obsered adversed effect value (NOAEL) is 695.13 mg/kg bw/day for effect on clinical signs and weight studied. Based on this value it can be concluded that piperazine adipate is not the reprotoxic substance.

Executive summary:

Based on the prediction done for piperazine adipate for two generation reproduction toxicity on rats, the esstimiated No obsered adversed effect value (NOAEL) is 695.13 mg/kg bw/day for effect on clinical signs and weight studied. Based on this value it can be concluded that piperazine adipate is not the reprotoxic substance.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

695.13 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

K2 data predicted using the QSAR toolbox version 3.0

Additional information

Justification for selection of Effect on fertility via oral route:

Based on the prediction done for piperazine adipate for two generation reproduction toxicity on rats, the esstimiated No obsered adversed effect value (NOAEL) is 695.13 mg/kg bw/day for effect on clinical signs and weight studied. Based on this value it can be concluded that piperazine adipate is not the reprotoxic substance.

Effects on developmental toxicity

Link to relevant study records

Reference

Endpoint:

developmental toxicity

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 gideline 415:one- or two- (or multi-) generation studies;OECD TG 422;OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

QSAR prediction is done using the QSAR toolbox version 3.0

GLP compliance:

not specified

Species:

other: rat;rabbit

Strain:

other: CD-1;Slc:SD;Charles River CD rats;New Zealand White

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

water

Duration of treatment / exposure:

day 6 to day 20

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:

Basis:
nominal in diet

Dose descriptor:

NOAEL

Effect level:

366 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Remarks on result:

other: not specified

Abnormalities:

not specified

Localisation:

not specified

Description (incidence and severity):

not specified

Dose descriptor:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Abnormalities:

not specified

Localisation:

other: not specified

Description (incidence and severity):

not specified

Developmental effects observed:

not specified

Treatment related:

not specified

The prediction was based on dataset comprised from the following descriptors: NOAEL
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" ) )

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 Non binder, non cyclic structure AND Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Weak binder, NH2 group OR Weak binder, OH group by Estrogen Receptor Binding

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 Michael addition OR Michael addition >> Acid imides OR Michael addition >> Acid imides >> Acid imides-MA OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes 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"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.482

Domain logical expression index: "i"

Parametric boundary:The target chemical should have a value of log Kow which is <= 0.19

Conclusions:

Based on the prediction done forpiperazine adipate for developmental toxicity on rats, the esstimiated No obsered adverse effect value (NOAEL) is 366 mg/kg bw/day for effect on body weight and Maternal Preg Loss. Based on this value it can be concluded thatpiperazine adipate is not the toxic substance for above dose.

Executive summary:

Based on the prediction done forpiperazine adipate for developmental toxicity on rats, the esstimiated No obsered adverse effect value (NOAEL) is 366 mg/kg bw/day for effect on body weight and Maternal Preg Loss. Based on this value it can be concluded thatpiperazine adipate is not the toxic substance for above dose.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

366

Study duration:

subchronic

Species:

rat

Quality of whole database:

K2 data predicted using the QSAR toolbox version 3.0

Additional information

Justification for selection of Effect on developmental toxicity: via oral route:

Based on the prediction done forpiperazine adipate for developmental toxicity on rats, the esstimiated No obsered adverse effect value (NOAEL) is 366 mg/kg bw/day for effect on body weight and Maternal Preg Loss. Based on this value it can be concluded thatpiperazine adipate is not the toxic substance for above dose. Also from the weight of evidence it is clear that from other source such as DEPA this substnace has negative effect on teratogenicity effect.