Piperazine

Endpoint summary

Description of key information

In a GPMT test only 1 out of 19 guinea pigs was positive (5%). Because of the questionable nature of this response, a second challenge was performed. Three of the nineteen animals exhibited clear responses; four additional animals had questionable responses. No response was seen in the ten control animals. Based on these responses in three of the nineteen animals (16%), Piperazine would be considered to be a mild sensitizer under the conditions of this study.

Piperazine was also studied in the Local Lymph Node Assay (LLNA). Groups of young adult Balb/c mice were administered piperazine at concentrations of 5, 10 and 20% (w/v). Piperazine (10%) produced a weakly positive response; a lack of effect at 20% was probably caused by local irritation and corrosion at this concentration.

Cytokine production was also studied. Mice were administered 50 μl piperazine at concentrations of 5 and 10% (w/v) on each shaved flank at days 1 and 6. At days 11, 12, and 13, daily doses of 25 μl were applied to the ears. The cytokine production was measured 13 days after initiation of treatment. Cytokine production (IFN-γ) was demonstrated, supporting that piperazine possess contact allergenic potential in mice. In the same study, piperazine failed to provoke production of IL-4 and IL-10, which are normally thought of as markers of respiratory tract allergens.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Although in studies with exposed workers piperazine has been shown to cause occupational asthma, as indicated above, cytokine production (IFN-γ) was demonstrated, supporting that piperazine possess contact allergenic potential in mice but in the same study, piperazine failed to provoke production of IL-4 and IL-10, which are normally thought of as markers of respiratory allergens. It could therefore be questioned whether piperazine should be considered an asthmagen (causing asthma by non-immunological mechanism) rather than a respiratory allergen (causing asthma by an immunological mechanism).

Justification for classification or non-classification

According to the harmonized CLP classification, piperazine should be classified as skin sensitizer cat. 1 (H317) and respiratory sensitizer cat. 1 (H334). In view of its low potency in the GPMT, viz. 5% positive result upon first challenge and 16% upon rechallenge (at 5% intradermal induction, 50% epicutaneous induction, and 25% epicutaneous challenge) and an EC3 value of 6.7% in the LLNA, and the failure of piperazine at test levels of 5 and 10% to provoke production of IL-4 and IL-10, which are normally thought of as markers of respiratory tract allergens, it can be concluded that in these animal tests, piperazine is of low potency which would warrant classification as cat. 1B for both skin and respiratory sensitization.