N,N'-diacetylhydrazine

Endpoint summary

Additional information

In Vitro

3 Ames tests are available one of which (Callander, 2004) was conducted rather closely to OECD TG 471. Although the result is considered to be valid, due to the lack of formal guideline and quality assurance, and very limited documentation, it should be regarded as not being reliable. This test gave a negative result both with and without activation using Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100 and Escherichia coli strains WP2 (pKM101) and WP2 uvrA (pKM101), applying the standard plate-incorporation assay protocol. This negative result is corroborated by the results from the independently conducted literature studies from Bhide (1984) (results also mentioned in Menon (1981), using TA 1535, TA 100, TA 98, TA 92 following in general OECD TG 471) and Tosk (1979) (using TA1535, TA100 and TA1530 following in general OECD TG 471).

 

The available studies are considered to be relevant and adequate for classification purposes. As a result, the data requirements for Regulation (EC) No. 1907/2006, Annex VII, 8.4.1, are considered to be met on the basis of the weight-of-evidence, in accordance with Annex XI, 1.2.

 

In Vivo

One relevant in vivo study was available addressing chromosome damage. In the study (Bhide, 1984) diacetylhydrazine was tested for its potential to cause chromosome damage in an in vivo micronucleus test in Swiss mice at 2400 mg/kg bw ip injected twice and conducted comparable to OECD 474. No adverse effects were seen at the tested dose, and the substance is deemed negative for in vivo chromosome damage in this test system. This study result was also cited in Mavourinin (1990).

 

Diacetylhydrazine was also tested for its potential to inhibit testicular DNA synthesis in the mouse in male Swiss mice after single ip injection of 3000 mg/kg bw. The treatment did not lead to an adverse effect as compared to the negative control. Accordingly, the substance is deemed negative for inhibition of testicular DNA synthesis in the mouse in this test system.

The studies are considered to be relevant, but not reliable because they were not performed according to a recognised guideline, nor under GLP, or with sufficient documentation.

Justification for selection of genetic toxicity endpoint
The endpoint is met on the basis of the weight of evidence.

Short description of key information:
- gene mutation in vitro: negative, Ames test, comparable OECD 471, Callander 2004, Menon 1981 & Bhide 1984, Tosk 1979
- chromosome damage in vivo: negative, comparable OECD 474, Bhide 1984 & and Mavourinin 1990
- murine testicular DNA synthesis inhibition: negative, no guideline, Menon 1981 & Bhide 1984

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The test item showed no genetic toxicity in any of the analysed endpoints bacterial gene mutation, chromosome damage in vivo and inhibit testicular DNA synthesis in the mouse. Other endpoints on genetic toxicity were not tested. Accordingly, the substance does not meet the criteria for classification according to commission Directive 2001/59/EC.

The test item showed no genetic toxicity in any of the analysed endpoints bacterial gene mutation, chromosome damage in vivo and inhibit testicular DNA synthesis in the mouse. Other endpoints on genetic toxicity were not tested. Accordingly, the substance does not meet the criteria for classification according to commission Regulation 1272/2008, Annex I, Part 3, 3.5