Registration Dossier

Administrative data

Description of key information

As indicated in the EU RAR (2005):

Groups of 15 MRC rats per sex were given 0.025% of piperazine in the drinking water (20 -25 mg/kg/day), 5 days/week, during 75 weeks after which the animals were kept until death and subjected to complete pathological examination. The dosed animals did not exhibit any increase of tumours in comparison with 15 male and 15 female controls (Garcia and Lijinsky, 1973).

When administered at 6.25 g/kg in the feed (about 938 mg/kg/day6) for 28 weeks and sacrificed at 40 weeks, it failed to induce any significant increase in the incidence of lung adenomas in groups of 40 Swiss mice per sex in comparison with controls (80 animals per sex) (Greenblatt et al., 1971). It is not possible to judge the extent of histopathologica examination performed upon autopsy, but in addition to lung adenomas, lymphomas, liver,

mammary glands, as well as sex organs seem to have undergone examination. The only significant finding was a reduction in the number of malignant lymphomas in the piperazine treated animals.  

Similar treatment of strain A mice with piperazine at 6.3 (938 mg/kg/day), or 18.8 g/kg (2,820 mg/kg/day) for 25 weeks, followed by a 13 weeks follow up post dosing, did not significantly increase the number of animals with lung adenomas. No histopathological analysis of other organs seems to have been performed (Greenblatt and Mirvish, 1973).

Available carcinogenicity studies with piperazine are scantily reported and do not meet present days' standards in most respects.

Key value for chemical safety assessment

Justification for classification or non-classification

Conclusion in EU RAR (2005):

Although there are no solid indications of a carcinogenic effect of piperazine, either in animal studies, or from the investigation in humans, the supporting database is insufficient to permit definite conclusions. However, in view of lack of genotoxic action, it appears unlikely that piperazine poses a carcinogenic risk.

Additional information