A Review of Nicotiana Tabacum L.

(Cultivated
Tobacco) and the Inhalation of its Combustion
Constituents via Tobacco Cigarette

Jacob C Donton
University of Idaho, Department of Chemistry, Environmental Chemistry 418, Dr. von Wandruszka, 8 May 2013

Abstract
Nicotine is a highly addictive compound which, when consumed for a period of time,
induces a chemical dependency.[1] This dependency causes psychosomatic and physiological
responses in the form of neuroadaptation.[1][3][4] As the brain and body become chemically
dependent on the nicotine, the cessation of its use is likely to cause a variety of withdrawal
symptoms, thus urging the user to maintain the intake of the nicotine. [1][2][5] Nicotine is one of
approximately 5300 compounds that are identified in cigarette smoke. [8][17] What is inhaled
through a filter from firsthand (mainstream) smoking and secondhand (sidestream) smoking,
differ.[8] Whether the exposure of tobacco cigarette smoke is mainstream or sidestream, the
adverse effects of both conduits are verily and indefinitely acknowledged. Neurological and
physiological responses are observed in animal and human subjects.[2][6][7][8]

Introduction of Health and Human Services have cited

Nicotiana Tabacum L. is the primary
strain of tobacco that is cultivated and
processed in the tobacco industry.[2] This
strain in particular contains a quantity of
nicotine that is responsible for the addiction
of tobacco and tobacco products, among
consumers.[10] The addiction to the nicotine
perpetuates the sales and thus is responsible
for the fiscal elevation of the tobacco
industry.[4][5][8][10] The industry of tobacco
has a global market, and with international
trade, it has amassed a large consumer-base.
[10]
Although the popularity of tobacco
cigarettes has tapered over the past decades,
there remains a consistent inflow of young
consumers.[2][10] The notion of a company
having a large consumer-base would be of
little concern were it not for the lethal nature
of the product. With this regard, the Centers
for Disease Control and U.S. Department
tobacco to be [the] single most important
preventable cause of premature death.[11]
Background:
Tobacco cultivation was thought to
have been in practice circa 5000-3000 BC in
the Americas.[12] European imperialism, via
Spain, was responsible for the fruition of
tobacco unto the European palate during the
1500s.[12] The spur of tobaccos popularity
was due in part from its perceived medicinal
qualities.[12] However much a truth, the
improper use and/or overuse of tobacco had
resulted in major health issues, then, and in
modern society.[10][11][12] Like many
medicinal substances, they are to be
employed properly and in moderation, and
not for recreational purposes. The factor of
addiction increased, when in the 1850s,
England produced the first cigarettes,
whereas pipe and snuff were the primary
methods of intake.[12] The manufacturing of
tobacco cigarettes allowed for the contents

University of Idaho, Department of Chemistry, Environmental Chemistry 418, Jacob Donton 1|Page
to be altered; additives that enhanced taste,
addictive properties, and potency.[12]
Concordantly, the method of biochemical
integration of the stimulant into the body
was made more efficient with the advent of
the cigarette.[12] The absorption of smoke
through the lungs resulted in a quicker and
more effective intake of nicotine,
conversely, elevating the lethality and toxic
nature of its smoke content.[12]
1. Pharmacodynamics: Chemistry of Addiction
Addiction is both a biochemical and
psychological response.[1] Such a response
can affect and physically alter brain
chemistry to cause a physiological need and
thus, a malicious reaction to the deprivation
of the stimulant.[1][2][3][7]
Fig. 1 [1]
Figure 1 demonstrates a 1988 report
from the Surgeon General regarding the
criteria for drug dependence. However
broad, it is the framework for the
identification of potentially dangerous
stimulants.[1][5]
Nicotinic acetylcholine receptors are
responsible for the processing of nicotine,
and for its neuroelectrochemical reaction.[1]
The reaction opens up channels for cations
to diffuse through, whereby the increased
concentration of cation increases the voltage
University of Idaho, Department of Chemistry, Environmental Chemistry 418, Jacob Donton
for that region, and thus, increased
stimulation.[1]
Fig. 2 [1]
Figure 2 portrays how the intake and
absorption of nicotine into the brain can
affect neurotransmitters.[1] Norepinephrine,
acetylcholine, serotonin, -aminobutyric
acid (GABA), glutamate, and endorphins are
the neurotransmitters which are triggered.[1]
These are powerful psychoactive chemicals
which can be over stimulated, causing
neural lesions on the synapses.[1] This form
of neuroadaptation causes a chemical
desensitization that is specific to these
nicotinic acetylcholine receptors, causing a
chemical dependence; disallowing self-
stimulation in lieu of external, supplemental
stimulation.[1][2][4][6] The saturation of the
neurotransmitters, if retained, causes a sense
of reward that drives the addiction.[5]
Fig. 3 [5]
Figure 3 is a diagram of the
mechanism behind the upregulation and
desensitization of neurotransmitters in the
nicotinic acetylcholine receptor complex.[5]
2|Page
The paths that are normal do not undergo the
levels of reactions that a disrupted and
upregulated path goes through.[5] The
disrupted path, if sustained via saturation of
stimulant, will cause an upregulated
reaction, amplifying the output of more
neurotransmitters.[5] This type of chain
reaction makes quitting the substance
excruciating. The brain becomes dependent
upon an upregulatory, acute exposure and
stimulation from nicotine, henceforth,
disrupting its natural pathways in order to
accommodate the intake of the nicotine.[5]
This creates a physical disallowance for the
cessation of nicotine intake, resulting in
serious physiological and psychological
repercussions.[1][3][5]
Fig. 4 [3]
Simplified schematic of the microcircuitry of ventral tegmental
area and NAc before and after smoking a cigarette. Shown are
excitatory and inhibitory synaptic inputs to the primary cell types
with the proposed cellular locations of nicotinic and muscarinic
receptors. On the left is the control situation, i.e. before the first
exposure to nicotine. On the right is the situation after 5 10 min
of nicotine exposure, at a concentration that is normally found in
the blood after smoking a single cigarette.
As shown in figure 4, the ventral
tegmental area and the nucleus accumbens
University of Idaho, Department of Chemistry, Environmental Chemistry 418, Jacob Donton
are locally affected and inhibited much like
the other, predominant nicotinic
acetylcholine receptors.[1][2][3][4][5]
Specifically, the occurrence is illustrated to
be the cholinergic modulation of
dopaminergic rewards areas of the brain. [3][5]
The reward areas of the brain are thus
affected and interfered with, causing an
effective desensitization and shift in the
brains chemical equilibrium.
Nicotine, if not regulated, physically
alters the brain, and monopolizes various
brain functions. In short, nicotine causes a
desensitization which incites the reward
complex, and concurrently, it creates a need
for itself via triggering an upregulation
complex.[1][5] The coupled effects create a
vicious cycle of what is known as a
chemical addiction.
2. Epidemiology/Health Economics
Tobacco cigarettes are known
culprits for many types of ailments and a
large number of deaths, worldwide. The
magnitude in which tobacco use has spread
has been steadily increasing over the years,
despite the increased awareness efforts
regarding the cessation of tobacco use.[13]
Fig. 5 [13]
The implications of a pandemic are
indicated in figure 5, as there is a stark
increase of tobacco use in all populations,
however more so for developing nations.[13]
Developing nations do not possess the same
capacity as developed nations, to fund and
delegate effective awareness campaigns.[13]
Adverse effects of tobacco are amplified
given, that in developing nations, there often
3|Page
lacks an effective central healthcare system.
[13]
The mobilization of healthcare is limited
to the available funds of a nation; turning
preventable ailments into a lethal bout with
death.[13]
Fig. 6 [14]
The lack of regulation for
advertisement regarding the marketing of
tobacco cigarettes, as shown in figure 6,
portrays a direct correlation between
awareness and per capita usage of cigarettes.
[14]
Each line coordinates to a country with
three types of campaigns for awareness:
weak to weak, weak to limited, and weak to
comprehensive.[14] The graph conveys that
with even a weak to limited campaign effort,
there is a large effect on the populations use
of tobacco cigarettes, over time.[14] This
would indicate that populations without any
sort of social medium to trigger an
awareness, simply do not know about the
true and real dangers of habitual tobacco
use, and may not have had a tobacco issue
early on. The graph shows that the weak to
weak campaign country conveys an initially
low per capita of smokers. There is a direct
increase in smokers in the weak to weak
countries when the countries with weak to
limited and weak to comprehensive
campaigns increase their awareness efforts.
[15]
As the weak to limited and weak to
comprehensive countries per capita of
smokers decreases, the weak to weak
countries are likely targeted by tobacco
University of Idaho, Department of Chemistry, Environmental Chemistry 418, Jacob Donton
industries, more than those with stronger
campaigns.[14][15] All together, the figure
illustrates the migration of the marketing of
tobacco from developed nations to
developing nations.[14][15]
Tobacco industries are attempting to
repudiate allegations regarding the findings
of the Governments on the Economics of
Tobacco Control (CTE) and the World
Health Organization (WHO).[15] The
findings elucidate the need for tobacco
control in developing nations while showing
that controlling tobacco does not have
serious economic stipulations.[15] The
International Tobacco Growers Association
(ITGA) argued that tobacco was important
to international economies and should not be
modulated so heavily.[15] The argument that
tobacco was vital for a developing countrys
economy had been proven invalid, so the
CTE and the WHO had retained
authoritative power when dealing with
global tobacco control.[15] Philip Morris
(PM), British American Tobacco (BAT), and
Japan Tobacco International (JTI) are
responsible for 41% of the international
tobacco market.[15] These companies form a
transnational grip over the economics and
regulation of tobacco, making it difficult for
localized regulation.[15] Laws must coincide
with each clause and protection act
regarding transnational trade and marketing.
[15]
Philip Morris funded a study for
$400,000 in twenty countries to prove that
tobacco was beneficial to their economies.[15]
The study was conducted by Arthur D. Little
International, concluding that the economic
benefit of tobacco was that the smokers die
early.[15] This report was cause for much
public criticism, which weakened the
tobacco industries credibility and influence
over tobacco control.[15] It was insinuated
that the only reason the tobacco industry
argued for lessening tobacco control, was
because their motives were to maximize
4|Page
profit.[15] They did not wish to help the
economies in which they sold to, but merely
make more money while the awareness
campaigns were nonexistent. The World
Bank and the WHO continue to attempt to
alleviate nations of the tobacco epidemic by
endorsing more communication with
populations regarding the health effects, as
well as having the power to stipulate
tobacco flow into a given country.
Although developed nations do have
serious issues with tobacco use, they are far
more susceptible to the health dangers.
Fortunately, there is an international effort to
Fig. 7 [16]
mitigate the wayward marketing of the
tobacco industry. Furthermore, extensive
research is being conducted regarding the
adverse health effects of tobacco products;
reinforcing and effort to cease if not ban
tobacco completely.
3. Toxicokinetics: Chemistry of a Cigarette
Nicotine is the primary cause of a
cigarettes addictiveness. However, it is not
the direct cause of its inherent lethality.[1][4][7]
[8][9][12]
Hydrocarbons remain in the cigarette
product from the industrial processing of
tobacco.[16]

A study from the Journal of Food

And Chemical Toxicology cited the
following chemicals to be carcinogenic to
humans by the International Agency for
Research on Cancer (IARC): Acetaldehyde,
Acrolein, Acrylonitrile, Benzo(a)pyrene (B(a)P), 1,3-
Butadiene, Cadmium, m- and p-Cresols (3- and 4-
methylphenol), Ethylene oxide, Formaldehyde,
Isoprene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-
butanone (NNK), N-Nitrosonornicotine (NNN), Vinyl
chloride.[15][16][17] These chemicals were
responsible for a wide variety of lesions in
mice, hamsters, and rats.[17]
Fig. 8 [17]
Compound Lesion
Acetaldehyde Nasal squamous cell carcinoma, Nasal
adenocarcinoma, Laryngeal squamous
metaplasia/ Hyperplasia, Nasal squamous
metaplasia, Nasal degeneration with
hyper/ metaplasia
Acrolein Disarrangement, necrosis, thickening and
desquamation of epithelium, Nasal
respiratory epithelial hyperplasia lateral
wall (II), Nasal respiratory epithelial
squamous metaplasia septum, Nasal
respiratory epithelial squamous
metaplasia septum
Acrylonitrile Lung adenoma or carcinoma,
Hyperplasia nasal turbinates,
Hyperplasia nasal mucous
secreting cells, Focal
Figure 7 makes apparent, the inflammation nasal turbinates,
Flattening of respiratory
contents of two common types of cigarettes, epithelium nasal turbinates
Benzo(a)pyrene (B(a)P) Tracheal tumours, Laryngeal
with regards to how their tobacco is tumours, Pharyngeal tumours,
processed.[16] Most, if not all of these Bronchioloalveolar
Tracheal tumour,
tumour,
Bronchial
compounds are carcinogenic. As outlined, a tumour, Laryngeal papillomas
and/or carcinomas
cigarette contains about 16.9-21.6mg of 1,3-Butadiene Alveolar/bronchiolar carcinoma,

these hydrocarbons per cigarette.[16] Alveolar/bronchiolar neoplasm,

Alveolar/bronchiolar epithelial

University of Idaho, Department of Chemistry, Environmental Chemistry 418, Jacob Donton 5|Page
 Hyperplasia
Cadmium Lung epidermoid carcinoma,
Lung adenocarcinoma, Total lung
carcinoma, Bronchioalveolar
adenomas, MesLaryngeal
epithelial degenerationenteric
lymph node inflammation, Nasal
respiratory epithelium, Alveolar
histiocytic infiltrate,
Tracheobronchial lymph
nodeinflammation , Nasal
olfactory epithelium
degeneration
m- and p-Cresols (3- and 4- Nasal goblet cell hyperplasia,
methylphenol) Nasal epithelial hyperplasia,
Nasal squamous metaplasia,
Nasal inflammation, Lung
bronchial hyperplasia, Nasal
respiratory epithelium glandular
hyperplasia
Ethylene oxide Alveolar/bronchiolar carcinoma or
adenoma, Alveolar epithelial
hyperplasia, Alveolar/bronchiolar
carcinoma or adenoma,
Pulmonary tumour
Formaldehyde Nasal squamous cell carcinoma,
Respiratory epithelium squamous
metaplasia, Nasal squamous Flow chart of fractionation of cigarette smoke condensate by liquidliquid
metaplasia/hyperplasia, Tracheal extraction. p, Precipitate; a, aqueous phase; o, organic phase., \ Fractions:
squamous metaplasia, Rhinitis, N&B, neutral and basic; W, water phase; S, sediment; N, neutral; BI, basic
Nasal focal respiratory epithelial and insoluble; BE, basic and ether-soluble; BW, basic and water-soluble;
keratinisation WAI, insoluble weak acid; WAE, ether-soluble weak acid; SAI, insoluble
Isoprene Alveolar/bronchiolar carcinoma, strong acid; SAE, ether-soluble strong acid; SAW, watersoluble strong acid;
Alveolar epithelial hyperplasia, WAP, phenolic weak acid; WAC, carbonated weak acid.
Nasal turbinate olfactory
epithelial
degeneration Figure 9 denotes the complexity and
4-(methylnitrosamino)-1-(3- Nasal tumours, Lung tumours,
pyridyl)-1-butanone (NNK) Lung adenomas, Nasal mucosa phases of the compounds found in cigarette
tumours, Respiratory tract
tumours
smoke, which suggestive of the
N-Nitrosonornicotine (NNN) Nasal tumours, Lung tumours, toxicokinetic variability.[7][17] This is an
Nasal cavity tumours, Tracheal
tumours, Malignant nasal indicator of the method of how the chemical
tumours
Vinyl chloride Bronchioalveolar adenoma, Lung will infiltrate, subjugate, deposit, and
angiosarcoma, Lung
bronchioalveolar tumours, Lung
interfere with the various chemical
hemangiosarcoma, Pulmonary processes present in the human body.[1][2][3][7]
tumours [17]
The sheer volume of lesions is an
Regardless of the danger level of
indicator of the toxicity of even a single
each individual compound, more research
cigarette, disregarding the smoking of many.
should be done on the constituents of
There are 5300 compounds in cigarette
cigarette smoke because there is highly
smoke.[17] The complexity of these
implicative research, present, that cigarettes
compounds compared against the complex
are highly carcinogenic.[1-17] There has been
nature of the human chemical equilibrium
limited research on the thousands of
would suggest that many chemicals may
chemicals present in cigarette smoke; due to
interact and affect the body in various ways.
[1][2][4][7][16][17] the sheer mass of chemicals.[3][4][5]
Contemporary research suggests that the
Fig. 9 [7]
dangers of the chemicals in cigarettes have
not been fully addressed, even though
exhaustive statistical and population
assessments indicate that cigarettes are
responsible for more than 5 million deaths
annually.

University of Idaho, Department of Chemistry, Environmental Chemistry 418, Jacob Donton 6|Page
Conclusion
Politics and economics play a crucial role when deciding the fate of any society. Tobacco
companies are free to market their product to any country, albeit, with some modes of control.
The peddling of drugs is nothing new for human societies. Tobacco is classified as a drug due to
its highly addictive quality and properties as a powerful psychoactive stimulant. The
neurochemistry is affected adversely, dictating and warping existing chemical equilibria;
essentially commandeering the brain via chemical subjugation. Tobacco cigarettes are highly
carcinogenic with regards to the industrial tobacco processing system. The amount of
compounds found within the smoke number upwards of 5000; each, potentially deadly. More
research must be done to mitigate the human losses, and to help the public be aware of when
they are partaking in, when smoking a cigarette.

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