Piperazine, compound with phosphoric acid

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

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

Data source

Reference

Reference Type:

other: predicted data

Title:

[R]: 1.36E3 mg/kg/day; Estimation for effect LOEL for CAS 1951-97-9

Author:

Sustainability Support Services (Europe) AB

Year:

2013

Bibliographic source:

QSAR Toolbox version 3.1

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

The prediction is done by using QSAR Toolbox Version 3.1

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Piperazine, compound with phosphoric acid

EC Number:

217-775-8

EC Name:

Piperazine, compound with phosphoric acid

Cas Number:

1951-97-9

Molecular formula:

C4H10N2.xH3O4P

IUPAC Name:

phosphoric acid; piperazine

Details on test material:

SMILES:C1CNCCN1_O=P(O)(O)O

Test animals

Species:

rat

Strain:

other: Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

5 (weeks/days)

Doses / concentrations

Remarks:

Doses / Concentrations:
160 - 1000 mg/kg/day
Basis:

Results and discussion

Effect levels

Dose descriptor:

other: effect LOEL

Effect level:

1 357.718 other: mg/kg/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: body weight decreased

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

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

Domain logical expression index: "a"

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

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 >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Acid anhydrides 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 Schiff base formation 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 on benzylic carbon atom OR SN2 >> Nucleophilic substitution on benzylic carbon atom >> Benzylic esters 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 by Protein binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Phtalate (or buthyl) diesters and monoesters (Nongenotox) OR Primary aromatic amine,hydroxyl amine and its derived esters (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 15 - Phosphorus P AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Group 17 - Halogens Cl OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.934

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= -0.632

Applicant's summary and conclusion

Conclusions:

In the estimated study lowest observed effect level (LOEL) value of piperazine, compound with phosphoric acid for repeated dose via inhalation route of exposure on rat is 1357.718 mg/kg/day.

Executive summary:

The estimated study lowest observed effect level (LOEL) value of piperazine, compound with phosphoric acid for repeated dose via inhalation route of exposure on rat is 1357.718 mg/kg/day.

In the other study used in the weight of evidence approach; repeated dose toxicity NOEL (No observed effect level) of piperazine, compound with phosphoric acid to mouse by the inhalation route was estimated at a dose concentration of 68.18 mg/kg bw/day. The summary of the two studies is presented below

S. No	Dose level	Species	Duration	Source of data
1	1357.718 mg/kg bw/day (LOEL)	Rat (Sprague-Dawley)	90 days	QSAR Toolbox version 3.1
2	68.1860 mg/kg bw/day (NOEL)	Mouse	91 days	QSAR Toolbox version 3.1