Allylamine

Description

Allylamine is a primary unsaturated alkylamine and in this review refers to monoallylamine. Allylamine can also be used generically to describe the secondary (diallyl-) and tertiary (triallyl-) amine derivatives of monoallylamine, as well as other more complex alkylamines. Allylamine is a colorless, flammable liquid and is volatile and reactive with oxidizing materials. Allylamine has a strong ammonia odor, is acutely toxic by all routes of exposure, and produces cardiotoxicity in a manner that has been well characterized by in vivo and in vitro methods. In addition to its use as an industrial chemical, allylamine is utilized as a model compound for basic research investigations into mechanisms of cardiovascular disease based on the nature of the cardiac and vascular lesions observed following allylamine exposure.

Chemical Properties

colourless liquid

Chemical Properties

Allylamine is highly reactive, combining the reactivity of amines with the unsaturation of the allyl group (Schweizer et al 1978). Reaction with halogens, for example, gives the corresponding halogenated propylamine in high yield.

Chemical Properties

Allylamine is a highly flammable, colorless liquid. Strong ammonia odor.

Uses

Allylamine is used as an industrial solvent and in organic synthesis, including rubber vulcanization, synthesis of ionexchange resins, and as an intermediate in pharmaceutical synthesis. Derivatives of allylamine are utilized as both veterinary and human pharmaceuticals, including the antifungal agent terbinafine. Allylamine has been used since the 1940s as a research tool for investigations of cardiovascular disease, with the earliest studies using allylamine to induce initial vascular injury in animal models of atherogenesis. Additionally, allylamine has been used to model myocardial infarction and vascular injury in animal models of human cardiovascular disease.

Uses

Allylamine ismanufactured fromallyl chloride andammonia. It is used as a solvent and in organic syntheses, including the synthesis of rubber, mercurial diuretics, sedatives, and antiseptics (238). It is also used in the synthesis of ion-exchange resins.

Uses

In the manufacture of mercurial diuretics.

Definition

ChEBI: Allylamine is an alkylamine.

Production Methods

Allylamine is produced by reaction of allyl chloride with ammonia. The amine is also a natural constituent of foodstuffs (Shumkova and Karpova 1981; Mochalov et al 1981) and is present in wastewater from oil shale retorting (Daughton et al 1985).

General Description

A colorless to light yellow colored liquid with a strong ammonia-like odor. Less dense than water. Vapors are heavier than air. Toxic by inhalation, ingestion and skin absorption. Irritates skin, eyes and mucous membranes. Flash point below 0°F. Boiling point 130°F. Used to make pharmaceuticals and other chemicals.

Air & Water Reactions

Highly flammable. Water soluble.

Reactivity Profile

Allylamine reacts violently with strong oxidizing agents and acids. Attacks copper and copper compounds [Handling Chemicals Safely 1980. p. 123]. Reacts with hypochlorites to give N-chloroamines, some of which are explosives when isolated [Bretherick 1979. p. 108].

Health Hazard

Acute: an eye, skin, and respiratory tract irritant, which is highly toxic if inhaled or ingested and moderately toxic if absorbed on skin. Ingestion or inhalation may cause death or permanent injury after very short exposure to small quantities. Skin absorption may cause irreversible and reversible changes. Toxic air concentration (TClo) in humans is 5 ppm over 5 minutes. Vapors are extremely unpleasant and may ensure voluntary avoidance of dangerous concentrations. Will irritate nose and throat at 2.5 ppm.

Health Hazard

Allylamine is a strong eye and respiratory tract irritant (Windholz et al 1983) and exposure to it causes transient irritation of mucous membranes of the nose, eye and mouth with lacrimation, coryza and sneezing (HSDB 1989). Exposure to 14 p.p.m. allylamine caused intolerable irritation of the eyes and respiratory tract (Grant 1974).

Fire Hazard

Flammable when exposed to heat, sparks, or flame. Vapor forms explosive mixtures with air over a wide range. Use caution when approaching fire and applying water. Vapor explosion and poison hazard indoors, outdoors or in sewers. Runoff to sewer may create fire or explosion hazard. Can react with oxidizing materials. When heated to decomposition, Allylamine emits toxic fumes. Avoid oxidizing materials. Stable, avoid heating to decomposition. May become unstable at elevated temperatures and pressures or may react with water with non-violent release of energy.

Flammability and Explosibility

Highly flammable

Industrial uses

Allylamine is used in the synthesis of ion-exchange resins and for water-dispersible copolymers useful for water purification and as flocculating agents (Schweizer et al 1978). The amine is also used for the preparation of pharmaceuticals including mercurial diuretics and antifungal agents (HSDB 1989).

Safety Profile

Poison by inhalation, ingestion, intraperitoneal, and skin contact routes. Human systemic effects by inhalation: lacrymation and lung effects. A systemic irritant. Mutation data reported. A severe eye and skin irritant. Extraordnary precautions against fumes are advised. Dangerous fire and explosion hazard when exposed to heat, flame, or oxidzers. Highly reactive. When heated to decomposition it emits toxic fumes of NOx. To fight fire, use alcohol foam, CO2, dry chemical. See also ALLYL COMPOUNDS and AMINES.

Potential Exposure

Compound

Environmental Fate

Allylamine exposure results in myocardial damage and intimal proliferation of vascular smooth muscle cells in multiple animal species. The mechanism for these distinctive cardiovascular lesions is believed to be related to its bioactivation to acrolein and possibly hydrogen peroxide. Several lines of evidence support this hypothesis; SSAO is highly active in vascular tissue where allylamine predominantly distributes, incubation of homogenates of vascular tissue with allylamine results in the generation of acrolein and hydrogen peroxide,and pretreatment with a semicarbazide inhibitor of SSAO reduces or eliminates the hypercontraction and vasospasm associated with allylamine exposure in vitro. Researchers have taken advantage of the distinctive lesions that result from various exposures to allylamine and have used it as chemical tool to induce animal models of cardiovascular dysfunction that resemble human disease.

Metabolism

The uptake, tissue distribution, excretion and pharmacokinetics of a 450 mg/kg oral dose of [¹⁴C]-allylamine has been studied over a 2 h period in male Sprague-Dawley rats (Boor 1985). The amine was rapidly absorbed from the gastrointestinal tract and quickly accumulated and then eliminated from tissues with a short halflife of less than 1 h that seemed to fit a one compartment model. The ¹⁴C-label was rapidly excreted in urine and no radioactivity was found in feces. Allylamine or its metabolites showed an unusual predilection for accumulating in elastic and muscular arteries with the highest radioactivity (5- to 10-fold higher than most other organs) occurring in the aorta. Radioactivity in all other tissues was generally much lower and fairly equal. At 5,10,15 and 20 min after an i.v. dose of [¹⁴C]-allylamine, 30 to 33% of the admitted radioactivity was localized in the aortas of adult Sprague-Dawley rats. By 30 min, 17% of the administered dose was still present in that tissue (Hysmith and Boor 1985). Upon differential centrifugation most of the radioactivity in the aorta was found to be localized in the mitochondria. Further in vitro investigations (Hysmith and Boor 1987) showed the specific binding of radioactivity from [¹⁴C]-allylamine to isolated rat aorta and heart mitochondria at both high affinity and low affinity binding sites. As much as 23 and 43% of the bound radioactivity was covalently linked to aorta and heart mitochondria, respectively. The monoamine oxidase B inhibitor, deprenyl, significantly reduced both the specific and covalent binding of radioactivity from [¹⁴C]-allylamine in phospholipase treated mitochondria while the benzylamine oxidase inhibitor, semicarbazide, had no effect on [¹⁴C]-allylamine binding. These results suggest that monoamine oxidase can convert allylamine to a highly reactive metabolite that selectively covalently binds to heart mitochondria and that this may explain the cardiotoxicity associated with this amine.
In vitro studies show that allylamine is converted by homogenates of various rat tissues (heart, aorta, skeletal muscle, lung) to acrolein (Boor et al 1981; Nelson and Boor 1982). Conversion of allylamine to acrolein in human tissue was 58, 8 and 6% in aorta, myocardium and liver, respectively, while in the rat the percentages of acrolein formation were 95, 18, 9 and 5% in aorta, lung, skeletal muscle, and heart preparations, respectively (Boor and Nelson 1982). Purified bovine plasma amine oxidase and porcine kidney diamine oxidase converted allylamine to acrolein in vitro (Nelson and Boor 1982). Studies with selective inhibitors suggested that benzylamine oxidase is the active enzyme in oxidizing allylamine. Inhibition of benzylamine oxidase with either semicarbazide or phenelzine protected aortic smooth muscle cells from allylamine-induced cytolethal injury (Hysmith and Boor 1988). Inhibition of benzylamine oxidase markedly altered the subcellular distribution of radioactivity from [¹⁴C]-allylamine in aortic smooth muscle cells, with the administered radioactivity no longer being localized in the mitochondria. The sole urinary metabolite of allylamine in vivo has been identified as 3-hydroxypropylmercapturic acid (Boor et al 1987; Kage and Young 1972). Parallel experiments showed glutathione (GSH) depletion in several organs, the most marked occurring in aorta, blood and lung. These findings indicate that allylamine was metabolized in vivo to the highly reactive aldehyde, acrolein, which was subsequently converted to a mercapturic acid through a GSH conjugation pathway.

Shipping

UN2334 Allylamine, Hazard class: 6.1; Labels: 6.1-Poison Inhalation Hazard, 3-Flammable liquids, Inhalation Hazard Zone B.

Purification Methods

Purify allylamine by fractional distillation from calcium chloride. It causes sneezing and tears. [Beilstein 4 IV 1057.]

Toxicity evaluation

The production and use of allylamine as an industrial solvent may result in environmental releases to the air, water, and soil.Allylamine is freely soluble in water, alcohol, chloroform, and most solvents. The vapor pressure at 20°C is 198mm Hg, the Henry’s law constant is estimated to be 9.95×10^-6 atm m3 mol^-1, and the octanol/water partition coefficient (log Kow) is estimated to be 0.21.

Incompatibilities

May form explosive mixture with air. Oxidizing materials and acids may cause a violent reaction. Attacks copper and corrodes active metals (i.e., aluminum, zinc, etc.).

Waste Disposal

High temperature incineration; encapsulation by resin or silicate fixation.