Azide, toxicity

Enzyme immunoassay (EIA) Buffer 0. M potassium phosphate buffer, pH 7.4, containing 0.1% BSA, 0 4A/NaCl, 0.001MEDTA, and 0 01% sodium azide (toxic). 

Sodium azide (toxic, Chapter 6, Secdon 2.3., Step 18). 

Buffer B 50 mMsodium phosphate buffer, 0.02% NaNg (sodium azide TOXIC ), pH 7.0. 

After many years of laboratory experience with various azides, the authors can report no occurrence of poisoning symptoms attributable directly to solid azides. However, with substances such as thallous azide, the physiological effects of thallium, in addition to the azide toxicity, are of equal concern. 

A. The mechanism of azide toxicity is unclear. Like cyanide and hydrogen sulfide, azide inhibits iron-containing respiratory enzymes such as cytochrome oxidase, resulting In cellular asphyxiation. Azide is also a potent, direct-acting vasodilator. 

B. Dermal. Industrial workers handling bulk sodium azide experienced headache, nausea, faintness, and hypotension, but it is unclear whether the exposure occurred via dermal absorption or inhalation. An explosion of a metal waste drum containing a 1% sodium azide solution caused bums over a 45% body surface area and led to typical azide toxicity with a time course similar to oral ingestion coma and hypotension developed within 1 hour followed by refractory metabolic acidosis, shock, and death 14 hours later. 

The manual is designed to allow the reader to move quickly from section to section, obtaining the needed information from each. For example, in managing a patient with isoniazid intoxication, the reader will find specific information about isoni-azid toxicity in Section II, practical advice for gut decontamination and management of complications such as seizures in Section I, and detailed information about dosing and side effects for the antidote pyridoxine in Section III. 

The best azide to use these days is sodium azide (NaNs). It is inexpensive and unwatched. All azides have the potential to explode upon degradation and are toxic to breathe. The methods... 

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. 

The Schmidt reaction of ketones works best with aliphatic and alicyclic ketones alkyl aryl ketones and diaryl ketones are considerably less reactive. The reaction is only seldom applied to aldehydes as starting materials. The hydrazoic acid used as reagent is usually prepared in situ by treatment of sodium azide with sulfuric acid. Hydrazoic acid is highly toxic, and can detonate upon contact with hot laboratory equipment. 

Caution The reaction should be carried out in a good hood because hydrazoic acid is very toxic. Care should also be taken in handling sodium azide. 

CAUTION All azides, particularly low molecular weight acyl and alkyl azides, are explosive, and great care should be taken while preparing and handling these materials. In addition, hydrazoic acid, which is liberated from unbuffered aqueous solutions of sodium azide, is highly toxic and all operations involving its use should be carried out in an efficient fume hood. 

The authors have also elaborated a microwave-enhanced one-pot procedure [90] for the Huisgen 1,3-dipolar cycloaddition reaction. In a typical procedure, a pyrazinone with a triple bond connected to the core via C - O linkage, was reacted with a suitable benzylic bromide and NaNs in presence of the Cu(I) catalyst in a t Bu0H/H20 system under microwave irradiation (Scheme 26). The cycloaddition was found to proceed cleanly and with full regioselectivity. As the azide is generated in situ, this procedure avoids the isolation and purification of hazardous azides, which is especially important when handling the ahphatic ones, which are known to be toxic and explosive in nature. 

In experiments where relatively small volumes of sediment suspensions are employed, autoclaving may significantly alter the structure of the sediment as well as introducing possibly severe analytical difficulties. In such circumstances, there are few alternatives to incubation in the presence of toxic agents such as NaNj, which has been used at a concentration of 2g/L. There remains, of course, the possibility that azide-resistant strains could emerge during prolonged incubation, and the possible occurrence of reactions between the substrate and azide must also be taken into consideration. 

A colorimetric procedure is described for the determination of small amounts of Compound 118 (1,2,3,4,10,10-hexa-chloro - 1,4,4a,5,8,8a - hexahydro - 1,4,.5,8 - dimethano-naphthalene). Reaction with phenyl azide to form a di-hydrotriazole derivative and subsequent treatment with diazotized dinitroaniline in strongly acid medium produce an intense red color. Amounts of the insect toxicant of 10 to 40 micrograms in the final 10-ml. aliquot are readily determined with a spectrophotometer. Commonly used insect toxicants do not interfere. 

Other applications dealt with the development of a luciferin ester substrate to measure the luciferase activity in living cells [141], the detection of toxic compounds such as sodium azide, fluoroacetic acid, and antibiotics [142], the development of a biosensor for the determination of bioavailable mercury [143], the use of eukaryotic luciferases as bacterial markers with different colors of luminescence [144], the determination of complement-mediated killing of bacteria [145], and the development of a bioassay for the determination of HIV type 1 virus and HIV-1 Tat protein activity, valuable also for analysis of HlV-inhibi-tory agents [146],... 

Indicine IV-oxide (169) (Scheme 36) is a clinically important pyrrolizidine alkaloid being used in the treatment of neoplasms. The compound is an attractive drug candidate because it does not have the acute toxicity observed in other pyrrolizidine alkaloids. Indicine IV-oxide apparently demonstrates increased biological activity and toxicity after reduction to the tertiary amine. Duffel and Gillespie (90) demonstrated that horseradish peroxidase catalyzes the reduction of indicine IV-oxide to indicine in an anaerobic reaction requiring a reduced pyridine nucleotide (either NADH or NADPH) and a flavin coenzyme (FMN or FAD). Rat liver microsomes and the 100,000 x g supernatant fraction also catalyze the reduction of the IV-oxide, and cofactor requirements and inhibition characteristics with these enzyme systems are similar to those exhibited by horseradish peroxidase. Sodium azide inhibited the TV-oxide reduction reaction, while aminotriazole did not. With rat liver microsomes, IV-octylamine decreased... 

Saxitoxin is a small tricyclic structure isolated from oceanic red tides it has attracted much interest for its peculiar structure and toxicity as a paralytic agent. The core structure that is related to a l-iminooctahydropyrrolo[l,2-f]-pyrimidine nucleus was prepared by rearrangement after oxidation of a double bond contained in a medium-size guanidine ring. This key intermediate in the synthesis was prepared from azide 376 with a judicious use of Mbs... 

The majority of the metal azides are sensitive explosives and exposure to heat, friction or impact is usually undesirable. Contact of most azides, particularly readily soluble ones, with acids will produce hydrogen azide, itself an explosive and highly toxic low-boiling liquid. In presence of heavy metals, it may give other equally hazardous heavy metal azides. These may also be formed from contact of soluble azides with heavy metals. 

Kit solution for the determination of toxic anions (e.g., arsenate, arsenite, azide, or cyanide) and other inorganic and organic anions with indirect UV detection... 

P25 Each of these [previous methods] involves one or more of the following drawbacks uses expensive and toxic metals, demonstrates severe water sensitivity, or produces hydrazoic acid, which is highly toxic and explosive as well as volatile. The few methods that seek to avoid hydrazoic acid liberation during the reaction, by avoiding acidic conditions, require a very large excess of sodium azide. In addition, ah of the known methods use organic solvents, in particular, dipolar aprotic solvents such as DMF. This is one of the solvent classes that process chemists would rather not use. (Adapted from Demko and Sharpless, 2001)... 

Sodium azide is a toxic as well as an explosive substance (Patnaik, P. 1999. A Comprehensive Guide to the Hazardous Properties of Chemical Substances, 2nd e(j New York John Wdey Sons). Although inert to shock, violent decomposition can occur when heated at 275°C. Contact of solid or solution with lead and copper must be avoided. Reactions with halogens, carbon disulfide, or chromyl chloride can be explosive. Dissolution in water produces toxic vapors of hydrazoic acid. The salt is an acute poison causing headache, hypotension, hypothermia, and convulsion. 

---