METHODS, AGENTS AND DEVICES FOR REMOVING NUCLEOPHILIC TOXINS FROM TOBACCO AND TOBACCO SMOKE

Abstract: This invention provides methods, devices and agents for the removal of nucleophilic toxins present in tobacco and tobacco smoke. The filter element of a tobacco smoking device or an air filtration device used in conjunction with a tobacco smoking device may comprise chemical moieties reactive with nucleophilic compounds, or agents that trap nucleophilic compounds may be incorporated into the filter element of tobacco smoking device such as a cigarette, cigar, pipe, or in a separate filter through which tobacco smoke passes before entering the mouth. The agents may also be incorporated into air filters for removing tobacco combustion product toxins from room air. The agents may also be incorporated into smoking or smokeless tobacco to remove toxins.

Description: 2 3 METHODS, AGENTS AND DEVICES FOR REMOVING NUCLEOPHILIC TOXINS 4 FROM TOBACCO AND TOBACCO SMOKE 5 6 FIELD OF THE INVENTION 7 This invention relates generally to methods, devices and agents for the removal of 8 nucleophilic toxins present in tobacco and tobacco smoke. Nucleophilic toxins are removed by the passage of tobacco smoke or air containing tobacco smoke through a nucleophilic lo toxin-removing filter device. Agents may also be incorporated into smolcing and smokeless π tobacco to prevent volatilization and absorption, respectively, of nucleophilic toxins. 1 Dosimetry of nucleophilic tobacco combustion products is used to monitor toxin exposure. 13 1 BACKGROUND OF THE INVENTION is Tobacco smoke is a complex mixture which includes numerous chemical compounds and 16 particulates which to a major extent are responsible for both the enjoyment of smoking and 17 the dangers to health in so doing. Use of tobacco products, especially smoking, is associated is with increased incidence of lung and other types of cancer, emphysema, and cardiovascular 19 disease. Less lethal adverse effects such as tooth discoloration and facial wrinkling also 20 occur. Among the many compounds present in tobacco smoke are the purported addictive 2i component nicotine, compounds responsible for flavor, and those either proven harmful or 22 believed to be harmful to human health. Tobacco smoke contains chemical toxins such as 23 carbon monoxide and hydrogen cyanide, and known carcinogens such as formaldehyde and 2 4 hydrazine. Specific compounds in tobacco smoke may fall into more than one of these 5 categories, such as those responsible for flavor. Methods for reducing the exposure of 1 smokers to these toxic compounds without affecting the flavor of smoke have been sought for 2 many decades. 3 4 The harmful effects of tobacco use, and principally cigarette smoking, derive from the 5 delivery to the body of toxic compounds present in tobacco and volatilized during its 6 combustion, as well as those formed as a result of combustion. These include gaseous 7 compounds, such as carbon monoxide, hydrogen cyanide, ammonia, and formaldehyde, and 8 others that are volatilized in tobacco smoke, such as benzene, acrolein, hydrazine, and aniline. 9 Collectively, the material which may be condensed from tobacco smoke is known as tar. lo Several compounds in smoke and tar are classified as carcinogens: benzene, 2- π naphthylamine, 4-aminobiρhenyl, and the radioactive element polonium-210. Others are 12 considered probable human carcinogens, such as formaldehyde, hydrazine, N- 13 nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine, benzo[a]pyrene, N- 14 nitrosodiethanolamine, and cadmium. Further compounds in tobacco smoke have been is proven to be animal carcinogens. While the carcinogenic potential of these tobacco smoke 16 components has never been tested directly in humans, a cause-and-effect relationship between π smoking and the aforementioned adverse effects has been strongly established through is epidemiologic studies. 19 20 Numerous methods and devices to reduce or remove toxic components from tobacco and 2i tobacco have been proposed and constructed. In general, a porous filter is provided as a first 22 line trap for harmful components, interposed between the smoke stream and the mouth. This 23 type of filter, often composed of cellulose acetate, both mechanically and by adsorption, traps 24 a certain fraction of the tar present in smoke. This type of filter is present on most cigarettes 1 available, yet it allows a significant amount of harmful compounds to pass into the mouth. 2 Epidemiological data connects use of filtered cigarettes with adverse health effects. 3 4 An improvement in the effectiveness afforded by a mechanical-type filter such as those 5 described above may be provided by including means for chemically trapping disagreeable 6 and harmful components present in smoke. For example, U.S. Patent 5,076,294 provides a 7 filter element containing an organic acid, such as citric acid, which reduces the harshness of 8 the smoke. A significant body of art focuses on removing formaldehyde, a prevalent 9 component of tobacco smoke with an established and adverse toxicological profile. U.S. lo Patent 4,300,577 describes a filter comprising an absorptive material plus an amine- π containing component which removes aldehydes and hydrogen cyanide from tobacco smoke. 12 U.S. Patent 5,009,239 describes a filter element treated with polyethyleneimine modified 13 with an organic acid, to remove aldehydes from tobacco smoke. U.S. Patent 5,850,840 14 describes the stabilizing of early glycosylation products in tobacco and tobacco smoke by is reaction with compounds such as acetaldehyde. U.S. Patent 4,246,910 describes a filter 16 impregnated with alkali ferrate compounds, or activated carbon or alumina impregnated with 17 potassium permanganate, for removing hydrogen cyanide from tobacco smoke. Control of is the delivery of tar, nicotine, formaldehyde and total particulate matter was afforded by a filter 19 element containing zinc thiocyanate, sarcosine hydrochloride, zinc chloride, ferrous bromide, 20 lithium bromide, or manganese sulfate, as describe in U.S. Patent 4,811,745. Inclusion of L- 2i ascorbic acid in a filter material to remove aldehydes is disclosed in U.S. Patent 4,753,250. 22 U.S. Patent 5,060,672 also describes a filter for specifically removing aldehydes, such as 23 formaldehyde, from tobacco smoke by providing a combination of an enediol compound, 24 such as dihydroxyfumaric acid or L-ascorbic acid, together with a radical scavenger of 1 aldehydes, such as oxidized glutathione or urea, or a compound of high nucleophilic activity, 2 such as lysine, cysteine, 5,5-dimethyl-l,3-cyclohexanedione, or thioglycolic acid. U.S. 3 Patent 5,706,833 describes a wet-disintegrable filter rod comprising certain water-soluble 4 polymers which serve as disintegrable adhesives. 5 6 As used throughout this application, the terms nucleophile and nucleophilic refer to a 7 negative ion or neutral molecule, such as an amino group or primary or secondary amine, that 8 brings an electron pair into a chemical reaction with another molecule or positive ion, called 9 an electrophile, which is capable of accepting the electron pair, such as an active carbonyl lo group. Nucleophilic compounds will chemically react with compounds bearing active π carbonyl groups, such as aldehydes, anhydrides, activated ketones, and active esters. 12 13 Smokeless tobacco includes tobacco products which are used by methods other than 14 smoking, for instance, as snuff and chewing tobacco. Toxic products present in tobacco also is enter the body by these methods of using tobacco which do not involve combustion, and 16 these products are also associated with numerous adverse sequelae of tobacco use. 17 is Contrary to the above-cited prior art in which nucleophilic compounds incorporated in a filter 19 were used to trap aldehyde-type toxins in tobacco smoke, it has been discovered that the 20 nucleophilic toxins present in tobacco and tobacco smoke may be removed from tobacco and 2i tobacco smoke by agents, or filters derivatized with chemical moieties comprising these 22 agents, which chemically trap nucleophilic compounds. Tar, mutagens, and known 23 carcinogens present in tobacco and tobacco smoke may be effectively removed by these 24 agents or filters comprising these agents which chemically traps nucleophilic toxins. Furthermore, agents which trap nucleophilic toxins may be incorporated into air filters to remove tobacco-derived toxins from room air, to reduce exposure to second-hand (sidestream) smoke. SUMMARY OF THE INVENTION The invention described herein provides a method for reducing the level of nucleophilic toxins present in tobacco or in mainstream and/or sidestream tobacco smoke by incorporating agents into the tobacco or passing the tobacco smoke through a filter element comprising agents which chemically react with and trap nucleophilic compounds present in tobacco combustion products. The agents may be admixed with smoking or smokeless tobacco. The filter element may comprise a porous filter matrix wherein the filter matrix bears chemical substituents which trap nucleophiles, or the filter may comprise a porous matrix and one or more agents that chemically trap nucleophiles. Agents with low vapor pressures and high melting points, such as insoluble, polymeric agents, are preferred for use in a smoking device filter. Furthermore, the nucleophile-trapping agents of the present invention may comprise or be incorporated into air filters for removing tobacco combustion product toxins from room air. Non-limiting examples of the types of agents that may be added to tobacco, or that comprise or may be incorporated into the filter of the present invention which traps nucleophiles include compounds belonging to the following classes: aldehydes, activated ketones, anhydrides, and active esters. The compound hematein may also be used. The methods, agents and devices of the present invention, while removing toxic nucleophilic compounds from tobacco and tobacco smoke, preferably do not detract from the flavor of the tobacco product. The agents and devices of the present invention may be used with i cigarettes, cigars, pipes, as well as in the form of separate filters placed between the tobacco 2 source and the mouth. Removal of toxic nucleophilic compounds from mainstream and 3 sidestream smoke are aspects of the invention. 4 5 For incorporation into smoking tobacco, suitable agents will trap nucleophiles present in the 6 tobacco or formed during burning, and not release them when the agent itself burns, during, 7 for example, the smoking of a cigarette. Agents incorporated into smokeless tobacco must be 8 of acceptable low toxicity and stability to achieve the trapping of nucleophilic toxins while 9 present within the oral cavity or other routes of exposure. 10 π Filters for use in tobacco smoking devices such as cigarettes or separate cigarette filters are 12 contemplated, as well as filters for use in air treatment or filtration systems through which 13 room or ambient air is actively or passively exposed, to remove nucleophilic toxins 14 therefrom. Such filters may range in size from the filter of a cigarette to replaceable filters is for commercial or industrial air handling systems. 16 17 Suitable filter matrices bearing substituents that may trap nucleophiles may include 18 periodate-oxidized (dialdehyde) derivatives of the polysaccharides cellulose, starch, agarose, 19 and partially-acetylated cellulose; or other polymers, resins or plastics of suitable porosity for 20 use as a tobacco smoke filter and derivatizable with aldehydic moieties. Alternatively, a 2i porous filter element such as a cigarette filter may be prepared which comprises an agent 22 capable of trapping nucleophilic toxins present in tobacco smoke. 23 Non-limiting example of aldehyde compounds that may be used as the agent in the porous filter or tobacco additive of the present invention include dialdehyde starch, dialdehyde cellulose, adenosine dialdehyde, inosine dialdehyde, O-phthaldialdehyde, aldehyde agarose, and ethylenedioxybis(3-benzaldehyde). Dialdehyde starch is preferred. Activated ketones useful in the practice of the present invention may include α-dicarbonyl compounds, β- dicarbonyl compounds, γ-dicarbonyl compounds, and α,β-unsaturated ketones. As non- limiting examples, α-dicarbonyl compounds may include camphorquinone, ninhydrin, phenylglyoxal, and alloxan; β-dicarbonyl compounds may include 5, 5 -dimethyl- 1,3- cyclohexanedione and dibenzoylmethane; γ-dicarbonyl compounds may include succinylphenone and hydrindantin; and α,β-unsaturated ketones may include 1,2- dibenzoylethylene, curcumin, and dicinnamalacetone. Non-limiting examples of anhydrides useful for the present invention include non-polymeric anhydrides such as 2-dodecen-l-ylsuccinic anhydride, bicyclo(2,2,2)oct-7-ene-2,3,5,6- tetracarboxylic dianhydride, diethylenetriaminepentaacetic dianhydride, ethylenediaminetetraacetic dianhydride, and (+)-diacetyl-L-tartaric anhydride. Non-limiting examples of active esters include N-α-t-butoxycarbonyl-L-alanine-N-hydroxysuccinimide ester, N-α-t-butoxycarbonyl-L-glutamic-α-benzyl ester-γ-N-hydroxysuccinimide ester, ε-t- butoxycarbonyl-aminocaproic acid N-hydroxysuccinimide ester, N-hydroxysuccinimidyl- modified agarose, and 6-aminohexanoic acid N-hydroxysuccinimidyl ester-modified agarose. N-hydroxysuccinimidyl-modified agarose is preferred. It is another object of the present invention to provide a device for reducing the levels of nucleophilic toxins present in tobacco smoke. The device may comprise a porous filter 1 matrix wherein the filter matrix bears chemical substituents which trap nucleophiles, or the 2 filter may comprise a porous matrix and one or more agents that chemically trap 3 nucleophiles. Agents with low vapor pressures and high melting points, such as insoluble, 4 polymeric agents, are preferred for use in a smoking device. Non-limiting examples of the 5 types of agents that may be used in the filter of the present invention include compounds 6 belonging to the following classes: aldehydes, activated ketones, anhydrides, and active 7 esters. The compound hematein may also be used. Non-limiting examples of agents capable 8 of chemically reacting with and trapping nucleophilic compounds present in tobacco smoke 9 are recited above. Passage of tobacco smoke through the device mechanically and lo adsorptively removes compounds and particulates, and the agent or moieties chemically react π with and trap nucleophilic compounds present in the tobacco smoke. 12 13 It is a further object of the present invention to provide a filter material which is capable of 14 reducing the level of nucleophilic toxins present in tobacco smoke passing through the filter, is the filter matrix bearing chemical substituents which trap nucleophiles. Suitable filter 16 matrices bearing substituents or moieties that may trap nucleophiles include periodate- 17 oxidized (dialdehyde) derivatives of the polysaccharides cellulose, starch, agarose, and is partially-acetylated cellulose; or other polymers or plastics of suitable porosity for use as a 19 tobacco smoke filter and derivatizable with aldehydic moieties. 20 2i It is yet another object of the present invention to provide an agent that can chemically trap 22 nucleophilic toxins present in tobacco smoke and may be included in a porous filter matrix. 23 Agents with low vapor pressures and high melting points, such as insoluble, polymeric 24 agents, are preferred. Non-limiting examples of the types of agents that may be used in the filter of the present invention include compounds belonging to the following classes: aldehydes, activated ketones, anhydrides, and active esters. The compound hematein may also be used. Non-limiting examples of suitable compounds are recited above. It is yet a further object of the invention to provide reduction in exposure of individuals to the toxic components in tobacco and tobacco smoke without reducing the enjoyment of using the tobacco products. It is yet another object of the present invention to provide a dosimetry device utilizing the agents of the present invention to provide an indication of the level of exposure to nucleophilic toxins present in the environment. These and other aspects of the present invention will be better appreciated by reference to the following drawings and Detailed Description. BRIEF DESCRIPTION OF THE DRAWINGS FIGURE 1 is a graph depicting a dose response of the removal of tar, measured colormietricaliy, from cigarette smoke by an agent and device of the present invention. FIGURE 2 is a graph depicting a dose response of the removal of tar, measured gravimetrically, from smoke from two different types of cigarettes by an agent and device of the present invention. FIGURE 3 depicts the removal of tar by a formulation of an agent of the present invention in the foπn of granules. FIGURE 4 depicts the removal of staining pigments from tobacco smoke by an agent and device of the present invention. FIGURE 5 depicts a dose response of the removal of mutagens from tobacco smoke by an agent and device of the present invention. FIGURE 6 depicts the removal of nitrosamines from tobacco smoke by an agent and device of the present invention. DETAILED DESCRIPTION OF THE INVENTION Of the numerous components heretofore identified in tobacco believed to contribute to the adverse consequences of smoking, direct toxins, human carcinogens, mutagens, probable human carcinogens and proven animal carcinogens are present. Human carcinogens include benzene, 2-naphthylamine, 4-aminobiphenyl, and the radioactive element polonium-210. Probable human carcinogens include such compounds as formaldehyde, hydrazine, N- nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopyrrolidine, benzo[a]pyrene, N- nitrosodiethanolamine, and cadmium. Further compounds in tobacco smoke have been proven to be animal carcinogens, including benz[a]anthracene, butyrolactone and N- nitrosonornicotine. Many of the aforementioned compounds are also directly toxic to cells in the body. While the toxicologic, mutagenic and carcinogenic potential of these tobacco smoke components has never been tested by direct experimentation in humans, a strong 1 cause-and-effect relationship between smoking and adverse effects has been established 2 epidemiologically. 3 4 Although smoking of tobacco, principally cigarette smoking, but also including cigar and 5 pipe smoking, is strongly linked epidemiologically to the aforementioned adverse sequelae, 6 exposure to smokeless tobacco products, including chewing tobacco and snuff, also carries a 7 risk of developing adverse health effects. Furthermore, smokers are principally exposed to 8 what is termed "mainstream" smoke, i.e, that which is inhaled from the smoking device. 9 However, recent studies have implicated exposure of nonsmoking individuals to what is o termed "sidestream" smoke, that which arises from the smoking device itself, with adverse i effects. The latter exposure has led to significant concern that individuals breathing "second- 2 hand" smoke are at risk for developing the same adverse health consequences that typify 3 smokers. Methods of removing toxic components from tobacco and especially tobacco 4 smoke, from mainstream and sidestream smoke, are desirable in reducing the excessive s health care costs associated with the consequences of tobacco and tobacco smoke exposure. 6 7 Reduction in exposure of individuals to the toxic components in tobacco and tobacco smoke s is desirable, without reducing the enjoyment of using the tobacco products. While the 9 removal or retention of nicotine is not a feature of the instantly-claimed methods or devices, 0 in one embodiment of the invention, retention of some or all of the nicotine content of the i smoke is desired. 2 3 Reduction in exposure of individuals to toxic compounds present in tobacco and tobacco 4 smoke may be achieved by the agents and device of the present invention at several points 1 along the route from the tobacco itself to the point of exposure by the individual. Agents may 2 be added to or blended into the tobacco itself, either smoking or smokeless tobacco, which 3 bind and sequester toxins, not permitting them to be leached or absorbed from the smokeless 4 tobacco or not permitting them to be volatilized into the smoke as the tobacco burns. For 5 smoking tobacco, a second stage of intervention is in removing toxic products from the 6 smoke stream. This may be achieved to some extent by toxin-sequestering agents added to 7 the tobacco itself, which before burning act as a filter. More useful is a filter placed between 8 the column of combusting tobacco and the mouth, or in a separate device, through which the 9 smoke passes before entering the body. By mechanical and adsorptive properties, present lo filters remove particulates, tar, and other components from the smoke. At a further stage, π exhaled tobacco smoke or sidestream smoke produced from the burning smoking device and 12 present in the environment may be filtered of toxins by passing ambient room air through or 13 in contact with a material or filter which removes toxins. 14 is As described above, porous, fibrous smoke filters remove a portion of these toxic compounds 16 by mechanical trapping and adsorption to the fibrous surface. Nevertheless, toxic 17 compounds remain in the inhaled smoke and contribute to enormous morbidity and mortality, is mainly lung and other cancers, other lung diseases such as emphysema, and cardiovascular 19 disease including heart attack and stroke. Numerous theories exist relating various 20 pathophysiological disease processes with specific tobacco smoke components. It is apparent 2i from this body of work that tobacco smoke contains toxins which are incompatible with 2 health, and that reduction of the exposure to the body of these toxins is prudent. Except for 23 abstaining from smoking and perhaps altering genetically the components in the tobacco leaf, 4 reduction in exposure of the smoker to tobacco smoke toxins may be achieved only by adding 1 toxin-sequestering agents to the tobacco or selectively removing toxins from the smoke 2 before inhalation. 3 4 On the other hand, it is desirable to not reduce the enjoyment of using tobacco products in 5 accordance with the objects of the present invention. 6 7 With the identification of significant amounts of the suspected carcinogen formaldehyde in 8 cigarette smoke, considerable effort has been expended by others on developing chemical 9 trapping methods for removing formaldehyde from smoke, mainly by including an aldehyde- lo trapping chemical in the filter. This may be achieved by the inclusion of nucleophilic π compounds in the filter, such as those containing amino groups, as cited in the Background 12 section above. Examples described above of filters incorporating nucleophilic compounds 13 such as lysine apparently have not achieved their desired effect as they have not been 14 commercially introduced. 15 16 It was found surprisingly and unexpectedly by the inventors herein that a significant 17 reduction in the level of mutagens and tar present in tobacco smoke may be achieved without is reduction in enjoyment of the product by the use of a filter which in addition to providing a 19 mechanical porous barrier, also traps nucleophilic compounds present in tobacco smoke. 20 Nucleophilic compounds present in tar and tobacco smoke include hydrazine and the i aromatic amines 4-aminobiphenyl, 2-naphthylamine, and aniline, among other compounds. 22 The aforementioned smoke components are known mutagens and known or suspected 23 carcinogens. Filter materials capable of trapping nucleophilic toxins from tobacco smoke 24 include a filter in which the filter matrix material bears nucleophile-trapping groups, such as aldehydic groups; alternately, one or more agents capable of trapping nucleophiles may be incorporated into the filter matrix. These toxins may also be removed by incorporating suitable nucleophile-trapping agents directly into the tobacco, and furthermore, these toxins may be removed from smokeless tobacco products by incorporating suitable nucleophile- trapping agents in the smokeless tobacco product. It is important to distinguish the intent of the nucleophilic-trapping methods, agents and devices of the present invention, which for example comprise aldehydic groups on a filter material, from the significant body of prior art in which electrophilic substances, such as aldehydes, were desirably removed from tobacco smoke by filters comprising nucleophiles. The present invention is essentially the reverse of the prior art. As an example encompassing the prior art, aldehydes in smoke were trapped by amino groups in or on filters; in the present invention, amines in the tobacco smoke are trapped by aldehydes in or on the filters. Suitable filter matrices bearing substituents that may trap nucleophiles may include periodate-oxidized (dialdehyde) derivatives of the polysaccharides cellulose, starch, agarose, and partially-acetylated cellulose; or other polymers, resins or plastics of suitable porosity for use as a tobacco smoke filter and derivatizable with aldehydic moieties. Agents that may be incorporated into a filter matrix capable of trapping nucleophilic compounds may be selected from aldehydes, activated ketones, anhydrides, and active esters. The compound hematein may also be used. Compounds are preferably of low vapor pressure in order to remain within the filter and not become volatilized on exposure to a stream of heated air and tobacco smoke. An insoluble, polymeric nucleophile-trapping agent is preferred. Suitable compounds for incorporation directly into smoking and smokeless tobacco products comprise those suitable for the intended purpose. For smokeless tobacco products, suitable agents must have a toxicological profile compatible with the extent of exposure to the individual, and furthermore not interfere with the taste, flavor, or enjoyment of the product. Compounds should be of low toxicity and preferably not absorbed. For incorporation into smoking tobacco to sequester nucleophilic toxins in the tobacco and that formed upon burning, the agents must not interfere with the flavor or enjoyment of the product, the rate of combustion of the smoking product either during or between inhalation, and not release the sequestered toxin when the agent within the tobacco is burned. Nucleophile-binding agents present in the tobacco act in part like a porous filter material for smoke passing through the as-yet unbixrned portion of the tobacco column. The presence of the toxin-removing material should not interfere with the draw, or resistance to passage of air and smoke, through the tobacco column or filter. Non-limiting examples of aldehyde compounds that may be used in the present invention include dialdehyde starch, dialdehyde cellulose, adenosine dialdehyde, inosine dialdehyde, O- phthaldialdehyde, aldehyde agarose, and ethylenedioxybis(3-benzaldehyde). Polymeric aldehyde compounds are preferred; of these, dialdehyde starch is preferred. Activated ketones may include α-dicarbonyl compounds, β-dicarbonyl compounds, γ-dicarbonyl compounds, and α,β-unsaturated ketones. As non-limiting examples, α-dicarbonyl compounds may include camphorquinone, ninhydrin, phenylglyoxal, and alloxan; β- dicarbonyl compounds may include 5,5-dimethyl-l,3-cyclohexanedione and dibenzoylmethane; γ-dicarbonyl compounds may include hydrindantin and succinylphenone; and α,β-unsaturated ketones may include 1,2-dibenzoylethylene, curcumin, and dicinnamalacetone. Non-limiting examples of anhydrides useful in the present invention include the non- polymeric anhydrides 2-dodecen-l-ylsuccinic anhydride, bicyclo(2,2,2)oct-7-ene-2,3,5,6- tetracarboxylic dianhydride, diethylenetriaminepentaacetic anhydride, ethylenediaminetetraacetic dianhydride, and (+)-diacetyl-l-tartaric anhydride. Non-limiting examples of active esters include N-α-t-butoxycarbonyl-L-alanine-N-hydroxysuccinimide ester, N-α-t-butoxycarbonyl-L-glutamic-α-benzyl ester-γ-N-hydroxysuccinimide ester, ε-t- butoxycarbonyl-aminocaproic acid N-hydroxysuccinimide ester, N-hydroxysuccinimidyl- modified agarose, and 6-aminohexanoic acid N-hydroxysuccinimidyl ester-modified agarose. N-hydroxysuccinimidyl-modified agarose is preferred. The foregoing agents may be prepared in various forms for incorporation into the filter element of the devices of the invention and for use in the methods of the invention. Such forms do not detract from the ability of the agents to bind nucleophilic toxins from tobacco smoke, but permit more facile manufacture of a suitable filter. Numerous methods known to one of skill in the art mayu be used to prepare the agent in a form suitable for incorporation into a filter, one non-limiting example being a granularized material prepared by comminution of a dried, extruded paste prepared from the agent, such as dialdehyde starch, and a binder, such as cornstarch. Alternate binding agents may include dialdehyde starch itself. 1 Prior uses of aldehydes in tobacco smoking articles has been limited to the inclusion of 2 aldehyde compounds as aroma or flavor modifiers. The compounds n-hexenal, n-octanal, n- 3 nonenal, n-decanal, n-tetradecanal, n-heptanal, n-undecanal, and n-dodecanal were 4 incorporated into the tobacco or filter material in accordance with U.S. Patent 4,627,449, in 5 order to improve the aroma and taste of the tobacco smoke and particularly the aroma of 6 sidestream smoke, i.e., the smoke which passes from the burning tobacco directly to the 7 environment. These compounds are volatilized from the tobacco into the smoke to mask the 8 adverse odors of burning cigarettes. Their vapor pressures make them unsuitable for use in 9 the present invention as they would be volatilized and lost from the filter and unable to trap lo nucleophiles from tobacco smoke. π 12 The preferred agent of the present invention is dialdehyde starch. Also known as oxidized 13 starch or polymeric dialdehyde, it is prepared by the periodate oxidation of starch, which 14 produces free aldehyde groups that may react with nucleophiles such as alcohols, amines, is hydrazines, hydrazides, and other reagents that condense with aldehydes. Dialdehyde starch 16 may be obtained from any of a number of chemical suppliers, such as Sigma Chemical 17 Company (Catalog No. P9265) or a manufacturer, Monomer-Polymer & Dajac Laboratories, is Inc. 19 0 Dialdehyde starch has been used previously for other applications, such as for increasing the i wet strength of paper, such as tissue paper; for hardening gelatin; for making water-resistant 2 adhesives; and for tanning leather. In enzyme studies, dialdehyde starch has been used to aid 23 in the attachment of proteins to polymer surfaces, by chemically reacting with hydroxyl 24 groups of a polymer film. It was further used directly as a polymer surface-modifying agent in U.S. Patents 5,281,660 and 5,563,215 to enable biologically active molecules and subsequently cells to bind to the modified surface without altering the biological properties of the molecules. Moderate heat treatment (50°C to 150°C) was necessary in order for the dialdehyde starch to bind to the polymer surface. Other agents suitable for the practice of the present invention may be selected from polymers such as agarose (e.g. SEPHAROSE(R)), cellulose, chitosan, dextran (e.g., SEPHADEX(R)), polyvinylpyrrolidone, and the like, which may be chemically derivatized to provide free nucleophile-trapping groups. For example, agarose may be derivatized to contain N- hydroxysucc rimidyl groups, such as Sigma Chemical Co. Catalog No. H8635, N- hydroxysuccimmidyl-activated SEPHAROSE(R) or Catalog No. A9019, 6-aminohexanoic acid N-hydroxysuccinimide ester coupled to SEPHAROSE(R). Aldehyde-agarose (Sigma Chemical Co. Catalog No. A9951) may also be used; one method of preparation involves derivatization of agarose with 4-aminobutyraldehyde diethyl acetal, and subsequent mild acid hydrolysis of the acetal to generate the aldehyde (Korpela and Hinkkanen, 1976, Analytical Biochem. 71:322-323). The insoluble polymers recited above may also be used directly as the filter material of the present invention. The device of the present invention may be prepared by any one of several methods known to the skilled artisan wherein the toxin-removing agent or agents are incorporated into an air filter or tobacco smoke filter at any of a number of stages in the manufacturing process. For example, an agent or agent so the present invention may be mixed with the raw material comprising the mechanical filter and then co-extruded or spun to form fibers comprising filter material and the toxin-removing agent, which may then be made into filters. Alternatively, extruded or spun fibers comprising the filter material may be coated with a molten agent or agents of the present invention, or a solution of the agent or agents in a suitable solvent, prior to the manufacture of the filters. In another process, the agent may be dissolved or suspended in a plasticizer and they sprayed onto the filter fibers. In another example, the filter devices of the present invention may be prepared from existing mechanical filters by preparing a solution or suspension of the agent or agents in a solvent, absorbing the solvent into the porous filter material, and then removing the solvent by evaporation, drying, freeze-drying, lyophilization, critical point drying, or another suitable method. The filter material would retain its mechanical properties as a barrier to particulate materials and an extensive surface to which tar may be adsorbed. hi another embodiment, an agent of the invention may be prepared in a granular foπn for incorporation into the filter of a smoking device. Binding agents such as cornstarch or gum arabic may be used to aid in the preparation of granules. In another embodiment in which dialdehyde starch is used as the nucleophilic-toxin-trapping agent, dialdehyde starch itself may be used as the binder to granulate dialdehyde starch in an active nucleophilic-toxin- trapping form. These and other means for preparing filter materials comprising an agent of the invention are embraced herein. In another embodiment, the filter material itself, for example, cellulose acetate, may be prepared and chemically derivatized to contain aldehyde groups, following standard methods. For example, cellulose may be partially acetylated or a certain percentage of the acetate groups on cellulose acetate may be hydrolyzed by treatment at high pH. The resulting partially-acetylated cellulose then may be subjected to periodate oxidation. Thus, the cellulose acetate may retain its fibrous and porous filter characteristics while also bearing aldehyde substituents capable of trapping nucleophilic toxins in tobacco smoke. Other polysaccharides with filter-like properties, such as cellulose, agarose, and the like may also be periodate treated to produce free aldehyde groups. Other polymers including plastics may also be chemically derivatized to produce aldehydic substituents. Preferably, the filter material will retain its mechanical filtration properties, by providing a mechanical barrier and extensive surface area to which tar may be adsorbed, in addition to its nucleophile-binding activity. For use in industrial or commercial air handing systems, air filters available for these systems to filter particulates and other air contaminants may be prepared which also contain an agent or agents of the present invention; alternatively the filter material itself may be derivatized or be prepared from an agent of the present invention, such that the air filter retains its mechanical filtration properties and in addition has the ability to remove nucleophilic toxins from the air. Similar filters or replaceable filter cartridges may be prepared for smaller units, such as those used to filter or purify the air in a single room or shared air space, automobile, bus, train, car, aircraft passenger compartments, racetracks, gambling and off-track betting parlors, bars, saloons, and similar areas in which tobacco products, especially smoking tobacco products, are used, and in some instances in which exposure to sidestream smoke is of particular concern to nonsmokers present therein. A personal air filtration system, similar in construction to a gas mask or face mask, may also be prepared using a filter device of the present invention, for individuals in proximity to such areas but seeking personal protection from the harmful effects of sidestream smoke. While the inventors do not wish to be bound by theory, the observation that aldehydes and other agents which chemically react with nucleophiles remove tar from tobacco smoke as will be seen in the following examples suggests that a significant portion of the toxic, mutagenic, and carcinogenic compounds present in tobacco smoke are nucleophiles. Of the established carcinogens known to be present in tobacco smoke, 4-aminobiphenyl, 2-naphthylamine, aniline, and hydrazine have primary amino groups. The data empirically show that the materials of the present invention also remove N-nitrosamines, but the mechanism of removal is not presently known. One would also reasonably expect that filter agent of the present invention would also remove hydrogen cyanide, which would react with the aldehyde groups to form cyanohydrins. The filter agent of the present invention would not be expected to remove aldehydes from tobacco smoke, such as formaldehyde, unless the compounds also possess a group which may be trapped by an aldehyde. However, trapping of amines by the filter agent of the present invention may produce new functional groups which may then be capable of absorbing, trapping, and chemically inactivating aldehydes and nitrosamines. It is another object of the present invention to provide a dosimetry device utilizing the agents of the present invention to provide an indication of the level of exposure of the device to nucleophilic toxins present in the environment. The device may be useful to individuals who work or live in an environment in which nucleophilic toxins such as those produced from tobacco smoke may permeate the air, and such individuals wish to gauge their exposure to such toxins. The device may also be useful to determine the proper time to change a filter used to remove nucleophilic toxins from the air. In one embodiment, the dosimeter is in the form of a wearable badge on which a disk or patch comprising an agent of the present invention is coated or therein incorporated. As the badge is exposed to environmental nucleophilic toxins, they chemically react with and adhere to the agent on the disk. As the nucleophilic toxins from tobacco smoke are brown-pigmented, the disk will darken in color with increasing exposure to nucleophilic toxins. A color comparison region on the dosimeter may be used to match the color and read out the level of exposure, based on a predetermined relationship between the disk color and toxin exposure. Other reagents may be included in the device to enhance color production as nucleophilic toxins bind to the agent, hi an another embodiment, a dosimeter device may comprise an air-collecting system, such as a pump or fan, which continually or upon activation introduces ambient air into one end of a transparent, graduated, open-ended column filled with a porous or granular filter material containing the agent of the present invention. Toxins present in the introduced air sample bind to the agent, initially proximally to the end of the column at which the air sample is introduced, and then, as the chemically reactive sites on the filter become bound with the toxin, additional toxin binds further along the column containing the agent, distally from the end of introduction. Because the nucleophilic toxins are pigmented, the length of the column of pigmented material present in the column, visually read from the column graduations, will indicate the amount of toxin present in the air. The graduations may be precalibrated depending on the rate of air sampling and the efficiency of sequestering pigmented toxins at the rate of air flow through the column. In a further embodiment, the amount of nucleophilic toxin bound to the agent within a dosimeter device may be determined by refiectometry to deteπnine pigment i color density, or by another detector means known to the skilled artisan for determining color 2- density or chemical derivatization. An automated device may provide an analog or digital 3 read-out of the ambient toxin level as a monitor of environmental quality, or be present to 4 indicate when a certain toxin level has been reached, for the purpose, for example, of 5 indicating when a toxin-removing air filter should be replaced with a fresh filter. Other 6 means for detecting a change in the physicochemical properties of the filter which is related 7 to the level of nucleophilic toxins bound to the filter, and other means for indicating the level 8 of nucleophilic toxins bound to the filter, are embraced herein. 9 o The column configuration of the agent and filter material of the present invention as i described in the dosimeter embodiment may also be used to determine the amount of filter 2 material necessary to effectively remove nucleophilic toxins from a particular smoking 3 device, in order to assist in the manufacture of smoking devices with reduced nucleophilic 4 toxins in the smoke. By drawing tobacco smoke through a calibrated column containing the s nucleophilic-toxin-binding agent of the present invention, the resulting length of pigmented 6 filter agent represents the amount of toxins present, and indicates the amount of filter material 7 that must be incorporated into a cigarette filter, for example, in order to effectively remove s toxins from the amount of tobacco present in the smoking device. 9 0 The agents and filter material of the present invention may also be used to measure the level i of nucleophilic toxins present in smoking or smokeless tobacco and other materials by using 2 the agents and filter materials of the present invention in a dipstick format. A predetermined 3 amount of porous filter material comprising an agent of the present invention may be 4 immersed in a suspension or extract of tobacco leaves, extracted cigarette filters, or another solution suspected of containing pigmented nucleophilic toxins in need of quantitating. After removal, the color intensity of the dipstick may be compared visually to known standards or electronically, by refiectometry, to a pre-established standard curve, to display the toxin level. The following examples are presented in order to more fully illustrate the preferred. embodiments of the invention. They should in no way be construed, however, as limiting the broad scope of the invention. EXAMPLE 1 Removal of Tar from Tobacco Smoke Measured Colorimetrically Cigarette smoke was filtered through 250 mg portions of each of the compounds listed in Table I. In order to achieve adequate draw with filters made from dialdehyde starch and oxidized starch, these compounds were deposited onto cellulose acetate fibers which had been spread out into swatches 0.25 by 3 inches. The treated fibers were then dried overnight at 37 C. The smoke from one cigarette was drawn through the filter material and then through 3 mis of distilled water using a water-pipe smoking device which was constructed from a 25 ml glass Erlenmeyer flask attached to a vacuum source with an air flow rate of approximately 35 ml/min. Three 100 microliter aliquots were removed from each flask, placed into ELIS A plate wells and read in an ELISA plate reader at 405 nm. The percentage or tar removed is based on a comparison between the cigarette comprising the filter containing the test agent and an appropriate control cigarette. The results are presented in the table below: To demonstrate the dose-response effect of increasing amount of an agent of the present invention in removing tar from tobacco smoke, cellulose acetate filter fibers were spread out into a swatch 0.25 inches by 3 inches and then coated with the following amounts of dialdehyde starch suspended in distilled water: 250 mg, 125 mg, 25 mg and 0 mg. The treated fibers were dried at 37 C overnight and then made into a tobacco cigarette using a tube cigarette maker. The smoke from 1 of each type of filter cigarette was then drawn through 3 mis of distilled water using a water-pipe smoking device which was constructed from a small (25 ml) glass Erlenmeyer flask attached to a vacuum source with an air flow rate of approximately 35 ml/min. Three 100 microliter aliquots were removed from each flask, placed into ELISA plated wells and read in an ELIS A plate reader at 405 nm. As shown in Figure 1, increasing amounts of dialdehyde starch resulted in an increased effectiveness of removal of tar from the tobacco smoke. EXAMPLE 2 Removal of Tar from Tobacco Smoke Measured Gravimetrically Cellulose acetate filter fibers were spread out into a swatch 0.25 inches by 3 inches and then coated with the following amounts of dialdehyde starch suspended in distilled water: 250 mg, 125 mg, 100 mg, 50 mg, 25 mg and 0 mg. The treated fibers were dried in a 37 C oven overnight and then made into a tobacco cigarette using a tube cigarette maker. The smoke from five of each type of filter cigarette was then drawn through 5 mis of acetone using a water-pipe smoking device which was constructed from a small (25 ml) glass Erlenmeyer flask attached to a vacuum source with an air flow rate of approximately 35 ml/min. After the cigarettes were burned the 5 mis of tar containing acetone was removed from each of the flasks and absorbed onto a pre-weighed disc of filter paper. Each flask was then rinsed with 1 ml of additional acetone two times. Acetone from the rinses was also absorbed onto the appropriate filter paper discs. Filter discs were dried overnight and then weighed. The 1 original pre-weight of the individual filter discs was subtracted from the final weight of the 2 individual filter discs to obtain the number of milligrams of tar obtained from each of the 3 filter cigarettes, and the results are expressed as percent of tar removed. 4 5 Figure 2 indicates that filters containing an agent of the present invention can remove over 6 90% of the tar from both "light" and "regular" tobaccos. If over 250 mg/filter is used, tar is 7 still removed, but the "drag" may be judged too difficult by the typical smoker. lo Example 3 n Preparation of Granular Dialdehyde Starch 12 13 Dialdehyde starch was prepared in granular form using various binders, examples of which 14 are described below. 15 16 1) Using cornstarch as a binder. Cornstarch (0.15 g) was suspended in 10 mis of distilled 17 water, heated to boiling for several minutes and then the mixture was allowed to cool to room is temperature. Dialdehyde starch (15 g) was mixed in and the resulting paste was extruded 19 through a #16 wire mesh. Two batches of extruded material were combined and dried 20 overnight at 70 C overnight and then lightly crushed to form granules. These were sized 2i through a #16 mesh, to give a material retained on a #30 mesh. These granules were then 22 dried at 70 C to a constant weight of 18 g. These granules had moderate resistance to 23 crushing. 24 2) Using gum arabic as a binder. The procedure described above in (1) was modified by using gum arabic (0.15 g) in place of cornstarch; also, the gum arabic was dissolved in the 10 ml of water at room temperature and was not heated prior to adding 15 g dialdehyde starch. Three batches of the resulting paste were combined and converted to granules as above, weighing 17.5 g after drying to constant weight. These granules had poor resistance to crushing. 3) Using dialdehyde starch as a binder. Dialdehyde starch (lOg) was suspended in 50 mis of distilled water. This solution was boiled for 2 hours until it became a clear yellowish paste. The paste was cooled to room temperature and divided into four 10 ml aliquots. The following amounts of dry dialdehyde starch was then blended into one of each of aliquots: 2 g, 5 g 10 g and 25 g. The materials were then dried at 37 C for 38 hours, and then crushed into granules. All of the different types of granules were sized through a #16 mesh to give a material retained on a #30 mesh. All granules were then dried at 37 C to a constant weight. All granules had moderate-good resistance to crushing. The ability of the granules prepared according to method 3 above to remove tar from cigarette smoke was evaluated as described in Example 2 above. "Regular" cigarette tobacco was used. As shown in Figure 3, increasing amounts of the granules showed a proportional increase in the removal of tar. EXAMPLE 4 Removal of Staining Pigments from Tobacco Smoke Cellulose acetate filters were spread out into swatches of 0.25 inches by 3 inches and then coated with 250 mg or 0 mg of dialdehyde starch suspended in distilled water. The treated fibers were then dried in a 37°C oven overnight and then made into a tobacco cigarette. The smoke from 2 of each type of cigarette was drawn into 1 ml of Phosphate Buffered Saline and the placed immediately on ice. Each sample was then applied to ELISA plate wells coated with 5% non-fat milk (100 microliters/well). Plates were incubated for 3 days @ 37 °C and then washed four times with 0.05% Tween/PBS. Pigments which remained bound to the wells were then solubilized in 100 microliters DMSO. Absorbance was then read at 405 mn. Results in Figure 4 show the average of three wells ± standard deviation. EXAMPLE 5 Removal of Mutagens from Tobacco Smoke A bacterial mutagenicity assay was performed as described by Ames et al. (Maron DM and Ames BN. 1983. Revised methods for the Salmonella mutagenicity assay. Mutation Research 113:173-215). Briefly, Salmonella strain TA98 was cultured overnight at 37 C in Oxoid nutrient broth #2, incubated with serial dilutions of cigarette smoke condensate from the following filter cigarettes: 250 mg dialdehyde starch/filter, 125 mg dialdehyde starch/filter, and 0 mg/filter diluted in 0.1 M sodium phosphate, pH 7.4 containing 33 mM KC1, 8 mM MgCl 2 , 5 mM glucose-6-phosphate, 500 micromolar NADP and rat liver S9 microsomal nucleases, in triplicate for 30 minutes at 37 C. The bacteria were then plated on minimal glucose plates. After a 48 hour incubation period at 37 C, the number of revertant mutants on each plate was counted. Each bar in the graph represents the average number of colonies on three plates ± standard deviation. Tester strain TA 98 detects frameshift mutations, such as those generated by aromatic primary amines. Mutagens in the sample are detected as the number of bacteria induced to revert to their wild-type phenotype. Figure 5 shows that increasing amounts of dialdehyde starch present in the cigarette filter result in a decrease in the mutagenicity of the smoke extract. Using the 250 mg filter, the number of revertants was no different than the negative control. EXAMPLE 6 Removal of Nitrosamines from Tobacco Smoke Cellulose acetate filter fibers were spread out into a swatch 0.25 inches by 3 inches and then coated with 250 mg of dialdehyde starch suspended in distilled water. The treated fibers were dried at 37 C overnight and then made into a tobacco cigarette using a tube cigarette maker. The smoke from one of each type of filter cigarette was then drawn through 3 mis of distilled water using a water-pipe smoking device which was constructed from a small (25 ml) glass Erlenmeyer flask attached to a vacuum source with an air flow rate of approximately 35 ml/min. Five hundred microliters of each sample was added to 500 microliters of each of the following solutions (1) 1% sulphanilic acid in 30% acetic acid (2) 0.1% naphthylamine in 30% acetic acid. The mixture was then incubated at 56 C. Samples were removed at 0, 10, 20 and 30 minutes and read a 540 nm using 620 nm as a reference value. Formation of color indicates the presence of nitrosamine compounds. Figure 6 shows that 250 mg of the agent of the present invention diminished the level of nitrosamines in the tobacco smoke extract by several fold. EXAMPLE 7 Taste Test A double-blind taste test was performed on 12 individuals in an office environment in a large city. The subjects were asked to fill out a brief questionnaire inquiring about their age, years of smoking, daily usage and preferred brand. After answering these questions, the subjects then lit two cigarettes, one with the filter of the present invention comprising dialdehyde starch, and one with a regular filter. As they smoked the cigarettes side by side, they were asked to record which cigarette was preferred and to describe any differences perceived between the two. The average age of the participants was 41 years, average duration of smoking 18.4 years, and each smoked on average 25.7 cigarettes per day. Eight of the twelve participants preferred the test cigarette with the dialdehyde starch filter over the control cigarette, and four individuals did not prefer one cigarette over the other. EXAMPLE 8 Analysis and Taste Test Cigarettes with cellulose acetate filters or with filters comprising an agent of the present invention were evaluated an independent laboratory for total particulate matter, nicotine, tar, water and carbon monoxide, according to the standardized FTC method. The cigarettes tested were made by treating cellulose acetate filters with 250 mg dialdehyde starch (DAS) in distilled water ("DAS Filter Cigarettes"). The treated fibers were dried overnight and incorporated into cigarettes using a tube cigarette maker. In this series of tests two types of control cigarettes were run: the standard "Kentucky Reference" cigarettes (provided by Lab Stat, Kitchener, Ontario, Canada) and "Ordinary Cigarettes" which were constructed in the laboratory of the inventors. Ordinary Cigarettes were constructed the same way as the filter cigarettes of the invention and they contain the same amount of tobacco and cellulose acetate fibers, but do not contain the filter additive. "Brand" Weight mα/ciq Puffs (per ciα) TP (mq/ciq) CO (mq/ciq) Water fmα/ciq) Nicotine (mq/ciq) Tar (mq/c Kentucky Reference 1069 8.6 11.3 13.2 0.892 0.831 9 Control Cigarette 986 8.7 17.99 15.8 3.245 1.056 13 DAS Filter t 1189 8.2 6.9 13.41 0.778 0.464 5 Cigarette The following results were obtained: The taste test was designed as follows: Subjects, n=20. Cigarette #1 = DAS filtered cigarette with a Marlboro ultralight tobacco column (detached from a store-bought Marlboro ultralight). Cigarette #2 = Marlboro ultralight cigarette (store bought). Both types of cigarettes had the same tar and nicotine ratings. The subjects were asked to fill out a brief questionnaire inquiring their age, years of smoking, daily usage and preferred brand. After answering these questions, the subjects then lit the two cigarettes, one with the DAS filter and a Marlboro Ultralight. Subjects were not given any information on the putative properties of the DAS filter other than that it was a new type of cigarette filter. As they smoked the cigarettes side by side, they were asked to decide how they would rate the tar and nicotine level in the DAS filtered cigarette, i.e., regular, light or ultralight. Results shown indicate that 58% of this group of smokers thought the DAS filtered cigarette was a regular cigarette, 33% thought it was a light cigarette and 8% thought it was an ultralight cigarette. Taken together the taste test results demonstrate that the DAS filtered cigarettes not only taste like ordinary cigarettes (unlike other "safer" cigarettes), but are also preferred by smokers. This invention may be embodied in other forms or carried out in other ways without departing from the spirit or essential characteristics thereof. The present disclosure is therefore to be considered as in all respects illustrative and not restrictive, the scope of the invention being indicated by the appended Claims, and all changes which come within the meaning and range of equivalency are intended to be embraced therein. It is to be understood that the devices of the invention is not limited to the description herein, which are deemed to be merely illustrative of the best modes of carrying out the invention, and which are susceptible of modification of form, size, arrangement of parts and details of operation. The invention rather is intended to encompass all such modifications which are within its spirit and scope as defined by the claims. Various publications in addition to the immediately foregoing are cited herein, the disclosures of which are incorporated by reference in their entireties.

Claims: WHAT IS CLAIMED IS: 1. A method for reducing the level of nucleophilic toxins present in air containing tobacco combustion products by passing said air through a filter element capable of removing nucleophilic toxins present in said air, said filter element comprising a polymer derivatized with aldehydic groups. 2. The method of claim 1 wherein said air comprises mainstream tobacco smoke and said smoke retains desirable flavor components after passage through said filter. 3. The method of claim 1 wherein said polymer is selected from the group consisting of periodate-oxidized cellulose, periodate-oxidized starch, periodate-oxidized agarose, periodate-oxidized partially-acetylated cellulose, and combinations thereof. 4. The method of claim 1 wherein said polymer derivatized with aldehydic groups is selected from the group consisting of dialdehyde starch, dialdehyde cellulose, and the combination thereof. 5. The method of claim 1 wherein said toxin-removing agent is dialdehyde starch. 6. A method for reducing the level of nucleophilic toxins present in air containing tobacco combustion products by passing said air through a filter element capable of removing nucleophilic toxins present in said air, said filter element comprising an agent selected from the group consisting of adenosine dialdehyde, inosine dialdehyde, o-phthaldialdehyde, ethylenedioxybis(3-benzaldehyde), and combinations thereof. 7. The method of claim 6 wherein said air comprises mainstream tobacco smoke and said smoke retains desirable flavor components after passage through said filter. 8. A method for reducing the level of nucleophilic toxins present in air containing tobacco combustion products by passing said air through a filter element capable of removing nucleophilic toxins present in said air, said filter element comprising an agent selected from the group consisting of activated ketones, non-polymeric anhydrides, active esters, hematein, and combinations thereof. 9. The method of claim 8 wherein said air comprises mainstream tobacco smoke and said smoke retains desirable flavor components after passage through said filter. 10. The method of claim 8 wherein said activated ketone toxin-removing agent is selected from the group consisting of α-dicarbonyl compounds, β-dicarbonyl compounds, γ- dicarbonyl compounds, and α,β-unsaturated ketones. 11. The method of claim 10 wherein said α-dicarbonyl toxin-removing agent is selected from the group consisting of camphorquinone, ninhydrin, phenylglyoxal, alloxan, and combinations thereof. 12. The method of claim 10 wherein said β-carbonyl toxin-removing agent is selected from the group consisting of 5,5-dimethyl-l,3-cyclohexanedione, dibenzoylmethane, and the combination thereof. 13. The method of claim 10 wherein said γ-cafbonyl toxin-removing agent is selected from the group consisting hydrindantin, succinylphenone, and combinations thereof. 14. The method of claim 10 wherein said α,β-unsaturated ketone toxin-removing agent is selected from the group consisting of 1,2-dibenzoylethylene, curcumin, dicinnamalacetone, and combinations thereof. 15. The method of claim 8 wherein said non-polymeric anhydride toxin-removing agent is selected from the group consisting of 2-dodecen-l-ylsuccinic anhydride, bicyclo(2,2,2)oct-7-ene-2,3,5,6-tetracarboxylic dianhydride, diethylenetriaminepentaacetic anhydride, ethylenediaminetetraacetic dianhydride, (+)- diacetyl-1-tartaric anhydride, and combinations thereof. 16. The method of claim 8 wherein said active ester toxin-removing agent is selected from the group consisting of bicyclo(2,2,2)oct-7-ene-2,3,5,6-hydroxysuccinimide ester, N-α-t-butoxycarbonyl-L-alanine-N-hydroxysuccinimide ester, N-α-t- butoxycarbonyl-L-glutamic-α-benzyl ester-γ-N-hydroxysuccinimide ester, ε-t- butoxycarbonyl-aminocaproic acid N-hydroxysuccinimide ester, N- hydroxysuccinimidyl-activated agarose, 6-aminohexyl N-hydroxysuccinimide ester- activated agarose, and combinations thereof. 17. A device for reducing the level of toxins present in air containing tobacco combustion products wherein said device comprises a filter element through which air passes, said filter element capable of removing nucleophilic toxins present in said air, said filter element comprising a polymer derivatized with aldehydic groups. 18. The device of claim 17 wherein said device filters mainstream tobacco smoke and said smoke desirable flavor components after passage through said filter. 19. The device of claim 17 wherein said polymer is selected from the group consisting of periodate-oxidized cellulose, periodate-oxidized starch, periodate-oxidized agarose, periodate-oxidized partially-acetylated cellulose, and combinations thereof. 20. The device of claim 17 wherein said polymer derivatized with aldehydic groups is selected from the group consisting of dialdehyde starch, dialdehyde cellulose, and the combination thereof. 21. The device of claim 17 wherein said toxin-removing agent is dialdehyde starch. 22. A device for reducing the level of toxins present in air containing tobacco combustion products wherein said device comprises a filter element through which air passes, said filter element capable of removing nucleophilic toxins present in said air, said filter element comprising an agent selected from the group consisting of adenosine dialdehyde, inosine dialdehyde, o-phthaldialdehyde, ethylenedioxybis(3- benzaldehyde), and combinations thereof. 23. The device of claim 22 wherein said device filters mainstream tobacco smoke and said smoke desirable flavor components after passage through said filter. 24. A device for reducing the level of toxins present in air containing tobacco combustion products wherein said device comprises a filter element through which air passes, said filter element capable of removing nucleophilic toxins present in said air, said filter element comprising an agent selected from the group consisting of activated ketones, non-polymeric anhydrides, active esters, hematein, and combinations thereof. 25. The device of claim 24 wherein said device filters mainstream tobacco smoke and said smoke desirable flavor components after passage through said filter. 26. The device of claim 24 wherein said activated ketone toxin-removing agent is selected from the group consisting of α-dicarbonyl compounds, β-dicarbonyl compounds, γ- dicarbonyl compounds, and α,β-unsaturated ketones. 27. The device of claim 26 wherein said α-dicarbonyl toxin-removing agent is selected from the group consisting of camphorquinone, ninhydrin, phenylglyoxal, alloxan, and combinations thereof. 28. The device of claim 26 wherein said γ-carbonyl toxin-removing agent is selected from the group consisting hydrindantin, succinylphenone, and combinations thereof. 29. The device of claim 26 wherein said α,β-unsaturated ketone toxin-removing agent is selected from the group consisting of 1,2-dibenzoylethylene, curcumin, dicinnamalacetone, and combinations thereof. 30. The device of claim 24 wherein said non-polymeric anhydride toxin-removing agent is selected from the group consisting of 2-dodecen-l-ylsuccinic anhydride, bicyclo(2,2,2)oct-7-ene-2,3,5,6-tetracarboxylic dianhydride, diethylenetriaminepentaacetic anhydride, ethylenediaminetetraacetic dianhydride, (+)- diacetyl-1-tartaric anhydride, and combinations thereof. 31. The device of claim 24 wherein said active ester toxin-removing agent is selected from the group consisting of bicyclo(2,2,2)oct-7-ene-2,3,5,6-hydroxysuccinimide ester, N-α-t-butoxycarbonyl-L-alanine-N-hydroxysuccinimide ester, N-α-t- butoxycarbonyl-L-glutamic-α-benzyl ester-γ-N-hydroxysuccinimide ester, ε-t- butoxycarbonyl-aminocaproic acid N-hydroxysuccinimide ester, N- hydroxysuccinimidyl-activated agarose, 6-aminohexyl N-hydroxysuccinimide ester- activated agarose, and combinations thereof. 32. The device of claim 17, 22 or 24 used to filter air in a tobacco smoke-generating device or in a tobacco smoke-containing environment selected from the group consisting of a cigarette, free-standing cigarette filter, pipe, cigar, air ventilation filter, gas mask, and face mask. 33. A method for preventing the absorption into the body of nucleophilic toxins present in smokeless tobacco by incorporating into said tobacco an agent capable of binding nucleophilic toxins present therein, said agent selected from the group consisting of a polymer derivatized with aldehydic groups, adenosine dialdehyde, inosine dialdehyde, o-phthaldialdehyde, ethylenedioxybis(3-benzaldehyde), activated ketones, anhydrides, active esters, hematein, and combinations thereof. 34. A device for monitoring the level of nucleophilic toxins in contact therewith comprising a nucleophilic-toxin-binding filter, means for detecting a change in the physicochemical properties of said filter which is related to the level of nucleophilic toxins bound to said filter, and means for indicating the level of nucleophilic toxins bound to said filter. 35. A method for reducing the level of nucleophilic toxins present in mainstream tobacco smoke derived from a tobacco-containing smoking device by incorporating into the tobacco of said device an agent capable of binding nucleophilic toxins present in said tobacco, said agent selected from the group consisting of a polymer derivatized with aldehydic groups, adenosine dialdehyde, inosine dialdehyde, o-phthaldialdehyde, ethylenedioxybis(3-benzaldehyde), activated ketones, anhydrides, active esters, hematein, and combinations thereof. 36. A method for reducing the level of nucleophilic toxins present in air containing tobacco combustion products by passing said air through a filter element capable of removing nucleophilic toxins present in said air. 37. The method of claim 36 wherein said air comprises mainstream tobacco smoke and said smoke retains desirable flavor components after passage through said filter. 38. The method of claim 36 wherein said filter element bears chemical substituents which trap nucleophiles. 39. The method of claim 38 wherein said filter element is a polymer derivatized with aldehydic groups. 40. The method of claim 39 wherein said polymer is selected from the group consisting of periodate-oxidized cellulose, periodate-oxidized starch, periodate-oxidized agarose, periodate-oxidized partially-acetylated cellulose, and combinations thereof. 41. The method of claim 36 wherein said filter element comprises an agent capable of removing nucleophilic toxins present in said air. 42. The method of claim 41 wherein said agent is selected from the group consisting of aldehydes, activated ketones, anhydrides, active esters, hematein, and combinations thereof. 43. The method of claim 42 wherein said aldehyde toxin-removing agent is selected from the group consisting of dialdehyde starch, dialdehyde cellulose, adenosine dialdehyde, inosine dialdehyde, O-phthaldialdehyde, ethylenedioxybis(3-benzaldehyde), and combinations thereof. 44. The method of claim 43 wherein said toxin-removing agent is dialdehyde starch. 45. The method of claim 41 wherein said activated ketone toxin-removing agent is selected from the group consisting of α-dicarbonyl compounds, β-dicarbonyl compounds, γ-dicarbonyl compounds, and α,β-unsaturated ketones. 46. The method of claim 45 wherein said α-dicarbonyl toxin-removing agent is selected from the group consisting of camphorquinone, ninhydrin, phenylglyoxal, alloxan, and combinations thereof. 47. The method of claim 45 wherein said β-carbonyl toxin-removing agent is selected from the group consisting of 5,5-dimethyl-l,3-cyclohexanedione, dibenzoylmethane, and the combination thereof. 48. The method of claim 45 wherein said γ-carbonyl toxin-removing agent is selected from the group consisting hydrindantin, succinylphenone, and combinations thereof. 49. The method of claim 45 wherein said α,β-unsaturated ketone toxin-removing agent is selected from the group consisting of 1,2-dibenzoylethylene, curcumin, dicinnamalacetone, and combinations thereof. 50. The method of claim 42 wherein said anhydride toxin-removing agent is selected from the group consisting of 2-dodecen-l-ylsuccinic anhydride, bicyclo(2,2,2)oct-7- ene-2,3,5,6-tetracarboxylic dianhydride, diethylenetriaminepentaacetic anhydride, ethylenediaminetetraacetic dianhydride, (+)-diacetyl-l-tartaric anhydride, and combinations thereof. 51. The method of claim 42 wherein said activated ester toxin-removing agent is selected from the group consisting of bicyclo(2,2,2)oct-7-ene-2,3,5,6-hydroxysuccinimide ester, N-α-t-butoxycarbonyl-L-alanine-N-hydroxysuccinimide ester, N-α-t- butoxycarbonyl-L-glutamic-α-benzyl ester-γ-N-hydroxysuccinimide ester, ε-t- butoxycarbonyl-aminocaproic acid N-hydroxysuccinimide ester, N- hydroxysuccinimidyl-activated agarose, 6-aminohexyl N-hydroxysuccinimide ester- activated agarose, and combinations thereof. 52. A device for reducing the level of toxins present in air containing tobacco combustion products wherein said device comprises a filter element through which air passes, said filter element capable of removing nucleophilic toxins present in said air. 53. The device of claim 52 wherein said device filters mainstream tobacco smoke and said smoke retains desirable flavor components after passage through said filter. 54. The device of claim 52 wherein said filter element bears chemical substituents which trap nucleophiles. 55. The device of claim 54 wherein said filter element is a polymer derivatized with aldehydic groups. 56. The device of claim 55 wherein said polymer is selected from the group consisting of periodate-oxidized cellulose, periodate-oxidized starch, periodate-oxidized agarose, periodate-oxidized partially-acetylated cellulose, and combinations thereof. 57. The device of claim 52 wherein said filter element comprises an agent capable of removing nucleophilic toxins present in said air. 58. The device of claim 57 wherein said agent is selected from the group consisting of aldehydes, activated ketones, anhydrides, active esters, hematein, and combinations thereof. 59. The device of claim 58 wherein said aldehyde toxin-removing agent is selected from the group consisting of dialdehyde starch, dialdehyde cellulose, adenosine dialdehyde, inosine dialdehyde, O-phthaldialdehyde, ethylenedioxybis(3-benzaldehyde), and combinations thereof. 60. The device of claim 58 wherein said toxin-removing agent is dialdehyde starch. 61. The device of claim 58 wherein said activated ketone toxin-removing agent is selected from the group consisting of α-dicarbonyl compounds, β-dicarbonyl compounds, γ- dicarbonyl compounds, and α,β-unsaturated ketones. 62. The device of claim 61 wherein said α-dicarbonyl toxin-removing agent is selected from the group consisting of camphorquinone, ninhydrin, phenylglyoxal, alloxan, and combinations thereof. 63. The device of claim 61 wherein said γ-carbonyl toxin-removing agent is selected from the group consisting hydrindantin, succinylphenone, and combinations thereof. 64. The device of claim 61 wherein said α,β-unsaturated ketone toxin-removing agent is selected from the group consisting of 1,2-dibenzoylethylene, curcumin, dicinnamalacetone, and combinations thereof. 65. The device of claim 58 wherein said anhydride toxin-removing agent is selected from the group consisting of 2-dodecen-l-ylsuccinic anhydride, bicyclo(2,2,2)oct-7-ene- 2,3,5,6-tetracarboxylic dianhydride, diethylenetriaminepentaacetic anhydride, ethylenediaminetetraacetic dianhydride, (+)-diacetyl-l-tartaric anhydride, and combinations thereof. 66. The device of claim 58 wherein said activated ester toxin-removing agent is selected from the group consisting of bicyclo(2,2,2)oct-7-ene-2,3,5,6-hydroxysuccinimide ester, N-α-t-butoxycarbonyl-L-alanine-N-hydroxysuccinimide ester, N-α-t- butoxycarbonyl-L-glutamic-α-benzyl ester-γ-N-hydroxysuccinimide ester, ε-t- butoxycarbonyl-aminocaproic acid N-hydroxysuccinimide ester, N- hydroxysuccinimidyl-activated agarose, 6-aminohexyl N-hydroxysuccinimide ester- activated agarose, and combinations thereof. 67. The device of claim 52 used to filter air in a tobacco smoke-generating device or in a tobacco smoke-containing environment selected from the group consisting of a cigarette, free-standing cigarette filter, pipe, cigar, air ventilation filter, gas mask, and face mask. 68. A method for preventing the absorption into the body of nucleophilic toxins present in smokeless tobacco by incorporating into said tobacco an agent capable of binding nucleophilic toxins present therein.

Inventors: CERAMI ANTHONY, CERAMI CARLA, ULRICH PETER, CERAMI, ANTHONY, CERAMI, CARLA, ULRICH, PETER
Applicants: CERAMI ANTHONY, CERAMI CARLA, CERAMI CONSULTING CORP, ULRICH PETER, CERAMI CONSULTING CORP., CERAMI, ANTHONY, CERAMI, CARLA, ULRICH, PETER
Application year: 2000
Main classification: A24D3
IPC codes: A24D3