And Dimethylhydrazine

This report is the second volume in the series Acute Exposure Guideline Levels for Selected Airborne Chemicals. AEGL reports for aniline, arsine, monomethylhydrazine, and dimethylhydrazine were reviewed in the first volume. AEGL documents for five chemicals—phosgene, propylene glycol dinitrate, 1,1,1,2-tetrafluoroethane, 1,1-dichloro-l-fluoroethane, and hydrogen cyanide—are published as an appendix to this report. The subcommittee... 

Reddy, B.S., Narisawa, T., Wright, P, Vukusich, D., Weisburger, J.H. Wynder, E.L. (1975) Colon carcinogenesis with azoxymethane and dimethylhydrazine in germ-free rats. Cancer Res., 35, 287-290... 

Goldin, B. R. and Gorbach, S. L. 1977. Alterations in fecal microflora enzymes related to diet, age, Lactobacillus supplements, and dimethylhydrazine. Cancer 40, 2421-2426. 

You probably spotted immediately that daminozide is again an amide, so the best disconnection is the C-N bond, which could take us back to acyl chloride and dimethylhydrazine. This time we ve written C-N amide above the retrosynthetic arrow as a reminder of why we ve made the disconnection and we advise you to follow this practice. 

In a study of hydrazine in aqueous systems, the chemical was reported to be absorbed by guppies from a 0.5 mg/L solution (Slonim and Gisclard 1976). After 96 hours, the hydrazine concentration in fish was 144 g/g, indicating a moderate tendency to bioconcentrate. However, the bioconcentiation of hydrazine and dimethylhydrazines is not expected to be important in aquatic systems because of the rapid degradation of these chemicals in water (see Section 5. 3.2.2) as well as their low octanol-water partition coefficients. 

Exposure of the general population to hydrazine and dimethylhydrazines is expected to be extremely low (WHO 1987). Because of the high reactivity of these chemicals, they are unlikely to remain in environmental media for extended periods. These chemicals have not been detected in ambient air, water, or soil. 

Physical and Chemical Properties. The physical and chemical properties of hydrazine and dimethylhydrazines are sufficiently well characterized to allow estimation of their environmental fate (see Table 3-2) (HSDB 1993 lARC 1975 Verschueren 1983). On this basis, it does not appear that further research in this area is required. 

Exposure Levels in Environmental Media. Hydrazine and dimethylhydrazines have not been detected in ambient air, water, or soil, since they are highly reactive and degrade readily in environmental media. Hydrazine and 1,1-dimethylhydrazine have been detected in workplace air and in tobacco (Cook et al. 1979 Schmeltz et al. 1977). Since these chemicals are highly reactive and exposure of the general population is not expected to be of concern, monitoring of ambient environmental media does not appear to be required. However, monitoring of workplace air would help to determine potential sources and magnitude of exposure. 

Exposure Levels in Humans. Hydrazine and dimethylhydrazines have not been detected in human tissues as a result of exposure to these chemicals from environmental media. Hydrazine has been detected in the urine of individuals taking medication (hydralazine) which may metabolize to hydrazine (Timbrell and Harland 1979). Since hydrazine and dimethylhydrazines are rapidly metabolized in vivo, it is unlikely that any free chemical would be present in biological tissues within a few days after environmental exposure. Studies that investigate the levels of hydrazines in humans within the first few days after exposure, along with their relationship to exposure levels, would be useful. This information is necessary for assessing the need to conduct health studies on these populations. 

Prior to GC or spectrophotometric analysis, hydrazine and dimethylhydrazines must be separated from the biological sample matrix and derivatives of the compounds must be prepared. Separation is usually effected by precipitation of residual protein with acid and extraction of interfering lipids with methylene chloride (Alvarez de Laviada et al. 1987 Preece et al. 1992a Reynolds and Thomas 1965 Timbrell and Harland 1979). Hydrazine and 1,1-dimethylhydrazine, but not 1,2-dimethylhydrazine, may then be derivatized with an aldehyde such as pentafluorobenzaldehyde or / -dimethylaminobenzaldehyde. 

Dimethylhydrazine, which has no free-Xt 1 group, cannot be derivatized in this way but may be quantified by chromatographic methods that do not require derivatization (Fiala and Kulakis 1981). Details of selected analytical methods for hydrazine and dimethylhydrazines in biological samples are summarized in Table 6-1. 

Accurate analysis of hydrazine and dimethylhydrazines in biological samples is complicated by the... 

Separation of hydrazine and dimethylhydrazines from environmental samples is by acid extraction when necessary. Air samples are usually collected in a bubbler with acid or on an acid-coated silica gel (NIOSH 1977a, 1977b, 1984). When GC is employed, detection may be by electron capture detector (ECD), FID, nitrogen-specific detector (NSD), thermionic ionization detector (TID), and/or MS as described above (Section 6.1). 

Accurate determination of hydrazine and dimethylhydrazines in environmental samples is also complicated by the susceptibility of these chemicals to oxidization. Air samples must be analyzed immediately after collection (Cook et al. 1979). Degradation of hydrazine in aqueous samples can be prevented by acidification with sulfuric acid (WHO 1987). 

Environmental Media. Analytical methods are available to detect and quantify hydrazine and dimethylhydrazines in air, water, soil, food, and tobacco (Amlathe and Gupta 1988 ASTM 1991b Holtzclaw et al. 1984 Leasure and Miller 1988 Liu et al. 1974 NIOSH 1977a, 1977b, 1984 ... 

In addition, methods are available to measure degradation products of hydrazine and dimethylhydrazines (see Section 5.3.2) in environmental samples and can be used to determine the environmental impact of these chemicals. 

Jaskiewicz K, Rossouw JE, Kritchevsky D, et al. 1986. The influence of diet and dimethylhydrazine on the small and large intestine of vervet monkeys. Br J Exp Pathol 67 361-369. 

Rutschmann MA, Buser HR. 1991. Determination of daminozide and dimethylhydrazine residues in Swiss apple juice concentrates using gas chromatography-mass spectrometry. J Agric Food Chem 39 176-181. 

Some toxic compounds (e.g., mitomycin C and dimethylhydrazine-2HCl), while they clearly increase the incidence of micronucleated erythrocytes after acute treatment, were not readily detected after multiple administrations, when integrated in general toxicity studies because the doses reached are much lower doses (Hamada et al. 2001). 

Determination of hydrazine, methylhydrazine, and dimethylhydrazine in liquid rocket fuels. 

A similar example, except one for which the product ions were directly affected by the dopant, was the simultaneous separation of peaks for ammonia, hydrazine, methylhydrazine, and dimethylhydrazine using nonanone. ° The ketone formed cluster ions with each of the available hydrogen atoms, and thus four ketone molecules were clustered on protonated hydrazine, three formed clusters with methylhydrazine, and just two formed them with dimethylhydrazine. The increase in mass and cross section to the core ion from the adducted ketones caused shifts in the drift time of the product ion peaks, so that clustered hydrazine had the longest drift time and dimethylhydrazine the shortest. This change in drift times is shown in Figure 11.2 with nonanone vapors near 1 ppm in the gas atmosphere throughout the drift tube. 

Ross, and R. A. Malt, Colostomy closure promotes cell proliferation and dimethylhydrazine-induced carcinogenesis in rat distal colon, Gastroenterol., 81 475-480 (1981). 

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