N,N'-diacetylhydrazine

Endpoint summary

Description of key information

- ADME in humans: bioaccumulation is not expected in humans, Ellard 1976
- metabolism in humans: plasma-halflife between 5 and 40 h, Lauterburg 1985a
- metabilism in humans: rapid acetylators metabolise a much smaller dose fraction to 14CO2 than slow acetylators, Lauterburg 1985b

Additional information

A couple of studies are available that touch the toxicokinetics of diacetylhydrazine in humans, though none of them explicitly focus on this substance. On the contrary, the results are usually present as supplement to analysis on the toxicokinetics of isoniazid or acetylhydrazine.

Ellard 1976 analysed absorption, distribution, metabolism and excretion of isoniazid and its metabolites in different experimental settings in humans. The single exposure was via the oral route with water as vehicle. In this entry only the results for diacetylhydrazine are regarded. Based on the development of urine levels diacetylhydrazine is absorbed to a high extent (> 77 %) in both volunteers after a dose of ca. 1.85 mg/kg bw. No metabolites of diacetylhydrazine are detected. All hydrazines detected are identical to the parent diacetylhydrazine. The half-life is ca. 5 h both in the slow as well as in the rapid acetylator. Therefore, bioaccumulation is not to be expected in humans.

In Lauterburg 1985a the toxicokinetics of isoniazid and its metabolites was analysed in humans. Overnight fasted human volunteers that have given informed consent were applied with 300 mg of isoniazid per oral (dissolved in water). Blood was sampled once 2 h post dosing and another 8 times until 35 h post dosing. Urine sampling was conducted up to 48 h post treatment. The plasma-halflife of diacetylhydrazine was found to be between 5 and 40 h in this experiment. All other results presented correspond to the toxikokinetics of isoniazid or acetylhydrazine.

Lauterburg 1985b regarded the toxicokinetic of isoniazid and its metabolites in humans. Overnight fasted human volunteers that have given informed consent were applied with 300 mg of isoniazid per oral plus 13 mg C14-labelled acetylhydrazine (dissolved in water). Blood was sampled at intervals for 4 h post dosing in all participants and for 36 h in 6 volunteers. Expired CO2 was analysed for the concentration of C14 (analysis period not stated). Rapid acetylators metabolise a much smaller dose fraction to 14CO2 than slow acetylators. All other results presented correspond to the toxikokinetic of isoniazid or acetylhydrazine.

The study from Iguchi, 1977, was disregarded as in this abstract, it was only stated that a GC-MS method was successfully established to quantify isoniazid, acetyl isoniazid, acetylhydrazine and diacetylhydrazine in human urine.

In summary, it can be stated that diacetylhydrazine is a metabolite inter alia of isoniazid and hydrazines. Results from Ellard (1976) showed that 1,2-acetylhydrazine is rather stable and its hydrolysis to acetylhydrazine is rather slow. After systemic absorption, which takes place with a high efficiency via the oral route (no data for the dermal or inhalation route, Ellard 1976) the substance is excreted rather quickly (half-life of 5 h, Ellard 1976). Accordingly, bioaccumulation is not to be expected in humans.