Piperazine, compound with phosphoric acid

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Piperazine (CAS No 110-85-0) is the parent molecule from which piperazine, compound with phosphoric acid or piperazine phosphate (CAS No 1951-97-9) is synthesized. In medicine piperazine is used in the form of the hexahydrate or as the citrate, tartrate, phosphate (1951-97-9) or adipate. Thus, piperazine and piperazine phosphate can be considered as belonging to the same category. No conclusive evidence of reproductive effects have been demonstrated in feeding studies with phosphoric acid or phosphate salts in various species of laboratory animal although limited studies have suggested testicular effects and reduced fertility in rats. No carcinogenic potential was demonstrated in limited feeding studies in rats treated with phosphoric acid or several of its salts, however, in rodents treated orally, several phosphates have been shown to promote the effects of known carcinogens. A wide range of genotoxicity assays (including the Ames bacterial test) have yielded essentially negative results with the acid or its salts. Based on the above, it is has been considered that the properties of piperazine (parent molecule) shall have an important influence on the toxicological properties of piperazine phosphate. Thus, Piperazine (CAS No 110-85-0) has been used as a read across substance, especially for the toxicological end points in this dossier preparation.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Salmonella mutagenicity test results for 250 chemicals.

Author:

Haworth S,Lawlor T, Mortelmans K, Speck W and Zeiger E

Year:

1983

Bibliographic source:

Environ. Mut. suppl. 1, 3-142.

Reference 2

Reference Type:

other: study report

Title:

European Union Risk Assessment Report : Piperazine

Author:

European Chemicals Bureau

Year:

2005

Bibliographic source:

3rd Priority List Volume: 56;Final Report, 2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Data is from Environ. Mut. suppl.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Piperazine

EC Number:

203-808-3

EC Name:

Piperazine

Cas Number:

110-85-0

IUPAC Name:

piperazine

Method

Species / strain

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 and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

piperazine tested at the concentrations 33, 100, 333, 1,000, or 2,167 μg/plate

Results and discussion

Test results

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Based on the in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 1535, TA 1537, TA 98, and TA 100 tested at the concentrations 33, 100, 333, 1,000, or 2,167 μg/plate with and without S9 metabolic activation it was found that Piperazine does not exhibit positive gene mutation effect.

Executive summary:

Based on the in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 1535, TA 1537, TA 98, and TA 100 tested at the concentrations 33, 100, 333, 1,000, or 2,167 μg/plate with and without S9 metabolic activation it was found that Piperazine does not exhibit positive gene mutation effect.