Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Hydrazine (JETOC 1996) and hydrazine monohydrate (MHLW 1996) were tested in the Ames test according to OECD TG 471 in the presence and in the absence of an additional metabolic activation system and yielded positive results.
Hydrazine was tested in the Mouse Lymphoma Assay in the absence of an additional metabolic activation system and proved to be a mutagen but mutagenicity was correlated with cytotoxicity (Rogers 1981)
According to OECD TG 473, hydrazine (JETOC 1996) and hydrazine monohydrate (MHLW 2003) were tested for chromosomal aberrations using Chinese Hamster Lung cells and yielded positive results. Hydrazine hydrate in human lymphocytes (Bayer AG 1990) showed no relevant chromosome aberrations.
In the mouse spot test according to OECD TG 484 the single intraperitoneal injection of 40 and 80 mg/kg bw hydrazine hydrate into pregnant female mice resulted in an non-significantly increased frequency of Spots of Genetic Relevance (SGR) but it was of biological relevance when compared to the historical control data of the performing institute (Bayer AG 1989). A study using the transgenic mouse model (Muta[TM] mouse) and the administration of a single oral dose of 400 mg/kg bw hydrazine sulphate, yielded negative results (Douglas 1995).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Additional information

Hydrazine, hydrazine monohydrate, and hydrazine hydrate yielded positive results when tested in the Ames test according to OECD TG 471 in the absence or in the presence of a metabolic activation system up to cytotoxicity. Tested in the Mouse Lymphoma Assay in the absence of metabolic activation hydrazine proved to be mutagenic but the mutagenicity was correlated with cytotoxicity. The in-vivo Mouse Spot Test yielded a non-significantly increased frequency of Spots of Genetic Relevance which was evaluated of biological relevance based on comparison with the historical control data of the performing institute only.

Hydrazine and hydrazine hydrate were tested for chromosome aberration in Chinese Hamster Lung cells. Both tests were performed according to the respective guideline in the presence and in the absence of metabolic activation and in concentration which ranges up to cytotoxicity. In both experiments chromosome aberrations were observed. Hydrazine hadrate was tested for chromosome aberration in human lymphocytes . The incubation time was 2 hours in the presence(+S9 -mix) and 24 hours in the absence (-S9 -mix) of a metabolic activation system. For evaluation the negative result of the chromosome aberration test in human lymphocytes it has to be taken into account that lymphocytes have to be stimulated with an exogen mitogen to undergo cell devision and that the cells in the presence of an additional metabolic activation system were incubated only for 2 hours instead of 3-6 hours as requested by the respective guideline.

In addition, there is an in-vivo MNT of limited validity performed with mice peripheral blood reticulocytes using different concentration levels of hydrazine hydrochloride and different dosing regimes: Mice received single intraperitoneal injections of 25, 50 or 100 mg/kg bw, or quadruple of 12.5, 25, 50 or 100 mg/kg bw, each 24 hours apart. The observed elevation of micronucleated reticulocytes showed neither dose-dependence nor relation to the expression time (Ohuchida et al 1995) and is therefore not regarded to provide reliable information. Hydrazine sulphate administered in a single oral dose of 400 mg/kg bw did not induce IacZ mutations in the lung, liver or bone marrow or transgenic mice sampled 14 and 56 days post treatment (Douglas 1995)

Overall, based on the available data, hydrazine showed evidence of a genotoxic activity, but the potential seems to be weak based on the fact that positive responses were not very pronounced and mainly in cytotoxic concentrations and that the in vivo studies do not give a clear positive response even at high doses.


Justification for selection of genetic toxicity endpoint
No individual endpoint study was selected. Overall, based on the available data, hydrazine showed evidence of a genotoxic activity, but the potential seems to be weak based on the fact that positive responses were not very pronounced and mainly in cytotoxic concentrations and that the in vivo studies do not give a clear positive response even at high doses.

Endpoint Conclusion: weak positive.

Justification for classification or non-classification

- Under Regulation No. 1272/2008 (GHS) the substance is not classified in a mutagenic category.