Toxicity hydrazine

The esters also react readily with aryl hydrazines to give aryl hydrazone derivatives. Examples of the latter were first synthesized (prior to the availability of tetraalkyl carbonylphosphonates) from tetraalkyl methylenebisphosphonates and aryl diazonium salts, analogously to the phosphonoglyoxylate hydrazone synthesis described in a previous section. First made as possible precursors in a ketone synthesis, several of these compounds, converted to free acid salts by treatment with BTMS followed by dicyclohexylamine in methanol, proved to have unexpected inhibitory activity vs the pyrophosphate-dependent phospho-fructokinase of the parasite T. gondii, which causes a potentially lethal opportunistic infection in immunocompromised persons such as AIDS patients [94]. In fact, the 2,4-dinitrophenylhydrazone of carbonylbisphosphonic acid (as the tetrasodium salt) dramatically abated toxoplasmosis lesions in infected human foreskin fibroblasts [94]. Animal toxicity in this compound, probably arising from in vivo hydrolysis to the highly toxic hydrazine, precluded its future development, but the result remains an interesting lead. 

One of the methods of choice for reduction of aromatic nitro compounds to the corresponding, synthetically important, aromatic amines is the use of hydrazine hydrate. Lu s group have developed a recoverable, recyclable polymer version of hydrazine hydrate that shows excellent activity, remaining very active even after eight cycles of use (Scheme 4.13), and avoiding the release of toxic hydrazine hydrate [58]. 

C10H17N3O5, Mr 259.26, amorphous powder, [ajp + 6.4° (H2O). A y-glutamyl compound from linseed (Linum usitatissimum). The toxic hydrazine derivative acts as a pyridoxine antagonist. ... 

The toxic hydrazine derivative N-formyl-N-methyUiydrazone of acetaldehyde, known as N -ethylidene-N-methylformohydrazide or gyromitrin (10-225), occurs in the fruiting body of false... 

Hydraziae is toxic and readily absorbed by oral, dermal, or inhalation routes of exposure. Contact with hydraziae irritates the skin, eyes, and respiratory tract. Liquid splashed iato the eyes may cause permanent damage to the cornea. At high doses it can cause convulsions, but even low doses may result ia ceatral aervous system depressioa. Death from acute exposure results from coavulsioas, respiratory arrest, and cardiovascular coUapse. Repeated exposure may affect the lungs, Hver, and kidneys. Of the hydraziae derivatives studied, 1,1-dimethylhydrazine (UDMH) appears to be the least hepatotoxic monomethyl-hydrazine (MMH) seems to be more toxic to the kidneys. Evidence is limited as to the effect of hydraziae oa reproductioa and/or development however, animal studies demonstrate that only doses that produce toxicity ia pregaant rats result ia embryotoxicity (164). 

Semicarbazide hydrochloride (hydrazine carboxamide hydrochloride) [563-41-7] M 111.5, m 173 (dec), 175 (dec), pK " 3.66. Crystd from aqueous 75% EtOH and dried under vacuum over CaS04. Also crystd from a mixture of 3.6 mole % MeOH and 6.4 mole % of water. [Kovach et al. J Am Chem Soc 107 7360 1985.] IR v 700, 3500 cm" [Org Synth Coll Vol I 485 I94I-, Davison and Christie J Chem Soc 3389 I955 -, Thiele and Stange Chem Ber 27 33 I894 pK Bartlett J Am Chem Soc 54 2853 1923]. The free base crystd as prisms from abs EtOH, m 96° [ Curtius and Heidenreich Chem Ber 21 55 1894]. TOXIC ORALLY, possible CARCINOGEN and TERATOGEN. 

NOTE - Petrochemical plants also generate significant amounts of solid wastes and sludges, some of which may be considered hazardous because of the presence of toxic organics and heavy metals. Spent caustic and other hazardous wastes may be generated in significant quantities examples are distillation residues associated with units handling acetaldehyde, acetonitrile, benzyl chloride, carbon tetrachloride, cumene, phthallic anhydride, nitrobenzene, methyl ethyl pyridine, toluene diisocyanate, trichloroethane, trichloroethylene, perchloro-ethylene, aniline, chlorobenzenes, dimethyl hydrazine, ethylene dibromide, toluenediamine, epichlorohydrin, ethyl chloride, ethylene dichloride, and vinyl chloride. 

Sodium azide (Eastman, 97-99%) is activated by dissolving 100 g of the salt in 400 ml of distilled water and stirring with 14 ml of hydrazine hydrate for 15 min. The solution is filtered and added dropwise to 4 liters of rapidly stirred, dry acetone. The solid is collected by filtration and washed with 150 ml of dry acetone. The fine powder (57-85 g) is dried under vacuum at 50° for 2 hr. Sodium azide is extremely toxic and the fine powder should be handled with care to avoid breathing the dust. 

Hydrazine, N2H4, is made commercially by this process. Certain byproducts of this reaction, notably NH2C1 and NHC12> are both toxic and explosive, so solutions of household bleach and ammonia should never be mixed with one another. 

Overall, DEHA is a low toxicity product, performs extremely well as a rapid oxygen scavenger and metal passivator, and is an excellent replacement for hydrazine. In addition, it is competitively priced and consequently a very popular product. 

CAUTION NOTE Hydrazine is toxic, and suitable precautions for its handling should be observed. Its use is usually prohibited in hospitals, the food manufacturing industry, and where steam may come into contact with food or beverages. The use of sodium sulfite may also be unacceptable in some of these applications. The existence of any regulations governing the use of either should be ascertained and observed. 

Household ammonia should never be mixed with chlorine bleach, because a redox reaction occurs that generates toxic chlorine gas and hydrazine NH3 + OCl —> CI2 + N2 H4 (unbalanced) Balance this equation. 

Recent studies have been directed towards the synthesis of heterocyclic hydrazones which have lower toxicities than thiosemicarbazones [44], It has been proposed that the hydrazinic N-H group is essential for activity since it might be involved in a crucial radical formation step important in the mechanism of RDR. This is supported by the loss of antileprotic activity for this series of compounds when the hydrazinic hydrogen is replaced by a methyl group [44]. The heterocyclic hydrazones, like thiosemicarbazones, behave as tridentate ligands. 

In the presence of excess ammonia, hypochlorite ion and ammonia can combine to form hydrazine (N2H4), another toxic and potentially explosive substance ... 

The hydrazine-aldehyde reaction has been used intracellularly to deliver non-toxic drug components, which when linked to form a hydrazone bond in situ, become cytotoxic (Rideout, 1986, 1994 Rideout et al., 1990). This same approach has been used to generate enzyme inhibitors in vivo, wherein the hydrazine and aldehyde precursors are not active, but when coupled together within cells to form a hydrazone linkage, become active site binders (Rotenberg etal, 1991). 

The hydrazine analogs P2H4, As2H4, and Sb2H4 are toxic and unstable, as indicated by the fact that P2H4 is spontaneously flammable in air, and phosphine burns readily. 

Given the toxic nature of hydrazine, it is clearly desirable to reduce the amount of hydrazine used in the spinning process. To this end, high-quality tin chalcogenide films spun using a mixture of water and hydrazine (20% hydrazine in water by volume) have also been demonstrated.47 The electrical properties of these films are comparable with those achieved from films deposited from pure hydrazine. 

Toxicological Profile for Hydrazines. 1997. U.S. Dept, of Health and Human Services (Agency for Toxic Substances and Disease Registry), Atlanta, GA. Accessed http //www.atsdr.cdc.gov/toxprofiles/tplOO.pdf. 

The comparative toxicity of hydrazine, and the symmetrical and asymmetrical isomers of dimethylhydrazine were reported by Jacobson et al. (1955). Rats and mice exposed to hydrazine, and rats exposed to symmetrical dimethylhydrazine exhibited restlessness, dyspnea, and convulsions with exophthalmos. Excessive salivation, vomiting, respiratory distress, and convulsions were reported for dogs exposed to asymmetrical dimethylhydrazine as well as monomethylhydrazine. Fourteen-day mortality in three groups of dogs (three dogs per group) exposed for 4 h to asymmetrical dimethylhydrazine at concentrations of 24, 52, or 111 ppm were 0/3, 1/3, and 3/3, respectively. For rodents, estimated LC50 values for hydrazine, asymmetrical dimethylhydrazine, and symmetrical dimethylhydrazine are shown in Table 3-8. 

Jacobson et al. (1955) noted that the toxic actions of hydrazine and its methylated derivatives were similar all are respiratory irritants and convulsants. However, monomethylhydrazine also induced severe intravascular hemolysis in dogs. 

Relative to other forms of hydrazine, House (1964) reported asymmetrical dimethylhydrazine to be less toxic to monkeys, rats, and mice. Mortalities over a 90-d inhalation exposure at 0.56 ppm (0.73 mg/m3) were 20%, 98%, and 99% for monkeys, rats, and mice, respectively. 

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