Svetlana Batyrbekova

A QSAR/QSTR study on the human health impact of the rocket fuel 1,1-dimethyl hydrazine and its transformation products: multicriteria hazard ranking based on partial order methodologies.

The possible impact of the rocket fuel 1,1-dimethyl hydrazine (heptyl) (1) and its transformation products on human health has been studied using (Quantitative) Structure Activity/Toxicity ((Q)SAR/(Q)STR) modelling, including both ADME models and models for acute toxicity, organ specific adverse haematological effects, the cardiovascular and gastrointestinal systems, the kidneys, the liver and the lungs, as well as a model predicting the biological activity of the compounds. It was predicted that all compounds studied are readily bioavailable through oral intake and that significant amounts of the compounds will be freely available in the systemic circulation. In general, the compounds are not predicted to be acutely toxic apart from hydrogen cyanide, whereas several compounds are predicted to cause adverse organ specific human health effects. Further, several compounds are predicted to exhibit high probabilities for potential carcinogenicity, mutagenicity, teratogenicity and/or embryotoxicity. The compounds were ranked based on their predicted human health impact using partial order ranking methodologies that highlight which compounds on a cumulative basis should receive the major attention, i.e., N-nitroso dimethyl amine, 1,1,4,4-tetramethyl tetrazene, trimethyl, trimethyl hydrazine, acetaldehyde dimethyl hydrazone, 1, 1-formyl 2,2-dimethyl hydrazine and formaldehyde dimethyl hydrazone, respectively.

Transformation products of 1,1-dimethylhydrazine and their distribution in soils of fall places of rocket carriers in Central Kazakhstan

In our research, three fall places of first stages of Proton rockets have been studied for the presence and distribution of transformation products of 1,1-dimethylhydrazine (1,1-DMH). Results of identification of transformation products of 1,1-DMH in real soil samples polluted due to rocket fuel spills allowed to detect 18 earlier unknown metabolites of 1,1-DMH being formed only under field conditions. According to the results of quantitative analyses, maximum concentrations of 1-methyl-1H-1,2,4-triazole made up 57.3, 44.9 and 13.3 mg kg(-1), of 1-ethyl-1H-1,2,4-triazole - 5.45, 3.66 and 0.66 mg kg(-1), of 1,3-dimethyl-1H-1,2,4-triazole - 24.0, 17.8 and 4.9 mg kg(-1) in fall places 1, 2 and 3, respectively. 4-Methyl-4H-1,2,4-triazole was detected only in fall places 2 and 3 where its maximum concentrations made up 4.2 and 0.66 mg kg(-1), respectively. The pollution of soils with transformation products of 1,1-DMH was only detected in epicenters of fall places having a diameter of 8 to10 m where rocket boosters landed. The results of a detailed study of distribution of 1,1-DMH transformation products along the soil profile indicate that transformation products can migrate down to the depth of 120 cm, The highest concentrations of 1,1-DMH transformation products were detected, as a rule, at the depth 20 to 60 cm. However, this index can vary depending on the compound, humidity and physical properties of soil, landscape features and other conditions. In the surface layer, as a rule, only semi-volatile products of transformation were detected which was caused by fast evaporation and biodegradation of volatile metabolites.

A QSAR/QSTR Study on the Environmental Health Impact by the Rocket Fuel 1,1-Dimethyl Hydrazine and its Transformation Products

QSAR/QSTR modelling constitutes an attractive approach to preliminary assessment of the impact on environmental health by a primary pollutant and the suite of transformation products that may be persistent in and toxic to the environment. The present paper studies the impact on environmental health by residuals of the rocket fuel 1,1-dimethyl hydrazine (heptyl) and its transformation products. The transformation products, comprising a variety of nitrogen containing compounds are suggested all to possess a significant migration potential. In all cases the compounds were found being rapidly biodegradable. However, unexpected low microbial activity may cause significant changes. None of the studied compounds appear to be bioaccumulating. Apart from substances with an intact hydrazine structure or hydrazone structure the transformation products in general display rather low environmental toxicities. Thus, it is concluded that apparently further attention should be given to tri- and tetramethyl hydrazine and 1-formyl 2,2-dimethyl hydrazine as well as to the hydrazones of formaldehyde and acetaldehyde as these five compounds may contribute to the overall environmental toxicity of residual rocket fuel and its transformation products.

Assessment of the mutagenic effect of 1,1-dimethyl hydrazine.

The mutagenic effect of the rocket fuel 1,1-dimethyl hydrazine has been studied experimentally and compared to the well-recognized mutagene N-nitroso dimethylamine. The manifestation of the effect for both compounds was disclosed through a significant increase in the chromosome aberration frequency in the bone marrow cells of intoxicated rats. The levels of chromosome aberrations induced by 1,1-dimetyl hydrazine were studied following both single (1h) and repeated doses (daily for 10 consecutive days) by inhalation (205-1028mg/m(3)) and gavage (5.4-26.8mg/kg) administration, respectively. For comparison N-nitroso dimethylamine were administered by inhalation (2h/daily for 10 consecutive days) and by gavage in concentrations of 2.4-48mg/m(3) and 1-30mg/kg, respectively. A clear dependence of concentration as well of time was disclosed. The BenchMark Dose approach was employed to derive guideline doses for the two compounds, the implications towards human health being discussed.