Toxicology- Questions and Answers

This article discusses the factors affecting toxicity, categories of toxins, adverse effects of toxins and their beneficial applications. It also covers the subject of tetrodotoxin and its therapeutic use in managing neuropathic pain.

Running head: TOXICOLOGY
Toxicology- Questions and Answers
Name of the Student
Name of the University
Author Note

1TOXICOLOGY
Answer 1
Toxicity refers to the degree of damage that a chemical substance can cause to an organism.
It refers to the adverse effects that are created on an entire plant, animal or microorganism, in
addition to those on cells and tissues (Jaishankar et al., 2014). Toxicity of a particular substance
is most commonly affected by a plethora of factors, which directly give rise to idiosyncratic
responses or unpredictable reactions. The major factors are as follows:
 Dosage, and the dose-time relationship
 Form of the substance and its innate chemical activity (Alomar, 2014)
 Exposure route (ingestion, inhalation or other routes)
 Life stage namely, infancy, youth and adulthood
 Species of the organism
 Gender of the person
 Drug absorption
 Drug metabolism
 Toxin distribution (Alomar, 2014)
 Health status such as, pregnancy organ function
 Circadian rhythm

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Gender plays a major role in influencing effects of a toxic chemical, by affecting the
pharmacokinetics and pharmacodynamics of the concerned drug (Llop et al., 2013). Exposure to
similar concentration of a toxin, for same duration will crate diverse effects on a middle aged
man and a woman based on the fact that the immune system plays a crucial role in protecting the
body from harmful toxins. The immune system acts as the target organ and its functions get
altered due to the effect of a toxin (Iwasaki & Medzhitov, 2015). Presence of a suppressed
immune system in the woman will predispose her to increased susceptibility of adverse health
outcomes. Furthermore, research evidences state that a suppressed immune system is more likely
to result in development of neoplastic diseases due to toxicity. In addition, the smoking habit will
also increase her likelihood of inhaling cancer-causing chemicals, the effect of which will get
aggravated upon exposure of the toxin by synergistic action (Sompayrac, 2015). Thus, deficiency
in immunological functions will result in development of recurrent, severe infections in the
woman.
Answer 2
Five broad categories of toxins are as follows:
Bacteria- Most bacterial toxins damage the cell wall of host organism, prevent protein
manufacture in the host cell, and stimulate immune response that damages the host. The most
common bacterial toxins are endotoxins, exotoxins, and enterotoxins.
 Endotoxins- These are natural and potentially toxic compounds, not secreted in any
soluble form. These structural components are released during lysis of bacterial cells
(Meseguer et al., 2014). e.g., lipo-oligosaccharide (LOS) and lipo-polysaccharide (LPS)
released from E.coli.

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 Exotoxins- These are potentially toxic soluble proteins that are responsible for disrupting
cellular metabolism, thereby damaging host cells (Greaney, Leppla & Moayeri, 2015).
e.g., released from Bacillus cereus and Vibrio cholera.
 Enterotoxins- These protein toxins target the intestinal cells and are chromosomally or
plasmid encoded. e.g., enterotoxin B produced by Staphylococcus aureus.
Algae- They release complex allelopathic chemical compounds called phycotoxins that affect
marine food web. The toxins are released upon their death.
 Phycotoxins- These metabolites are most commonly produced by macroalgae and
freshwater algae and result in severe health and economic impact upon humans (Anfossi
et al., 2013). e.g., toxins by dinoflagellates act on mussels, which if consumed can cause
illness.
Fungi- They most commonly produce natural products from molds that create toxic
responses on acting in small concentrations on vertebrates.
 Mycotoxins- They are toxic secondary metabolites produced by molds and are can even
lead to death in humans (Anfossi et al., 2013). e.g., alfatoxins produced by Aspergillus
sp. and Ochratoxin produced by Penicillium sp.
Plants- Most weeds, aromatic and ornamental plants produce secondary metabolites with
pharmaceutical and toxicological effects, commonly known as plant toxins. These are procusded
in addition to primary metabolites such as, lipids and carbohydrates (Ibanez, Gallet & Després,
2012).

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 Phytotoxins- The term encompasses substances that are most commonly produced by
plants and interfere with the functioning of the human physiological system. e.g., nicotine
from tobacco plant and ricin from Ricinus communis.
Animals- Toxins produced by animals are principally used for defense or predation. These
are bioactive compounds such as, proteins, enzymes, amines and steroids (Kalia et al., 2015).
 Zootoxins- It refers to the toxic substances that are produced during metabolism of higher
animals. e.g., toxins from shellfish and oysters.
Answer 3
Adverse effects caused by a chemical substance on an organism, occurs by different ways as
mentioned below:
 Cellular toxicity- Toxic chemicals most often perturb the homeostatis of a cell, resulting
in several succeeding events such as, reduction in ATP production, increased
permeability of the plasma membrane, thereby disrupting its integrity, and decrease in
growth factor. Most toxins result in death of the target cells after a considerable time
period, depending on the cell type, temperature, and stimulus type. The toxins also lead to
apoptosis where the cells shrink away and undergo a blebbing at the periphery
(Sgambellone et al., 2013). On the other hand, toxic effects also result in necrosis (cell
gets converted to debris that is removed by inflammatory response) and oncosis (swelling
of cells following an injury) of cells.
 Genetic toxicity- Some compounds, commonly known as genotoxic chemicals are
responsible of modifying hereditary materials, thereby affecting the intricate heredity
process. These toxins interact with the sequence and structure of DNA, thereby causing

5TOXICOLOGY
sudden alterations in the genetic material. This results in mutation, which may often lead
to cancer. These damages are permanent and affect either somatic or germinal cells,
thereby getting transferred to future generations. Research evidences suggest that
inherited defects in repairing damaged DNA results in cancer or developmental
abnormalities in childhood (Magdolenova et al., 2014). Most common toxins that result
in genotoxicity are aflatoxins and aromatic amines.
 Immunotoxicity- Interaction of the immune system with several xenobiotics most often
result in undesirable effects. While these toxins often suppress the immune system, at
times they also result in excessive or enhanced immune response such as, autoimmunity
or allergic reactions. Exposure of the immune system to toxins therefore results in an
increase in the incidence of neoplasia and other infectious diseases, due to inability of the
host cells to appropriately respond (DeWitt et al., 2012). Other effects include, rhinitis,
asthma, dermatitis, and other autoimmune diseases
 Target organ toxicity- Target organ toxins are chemical compounds that are responsible
for causing adverse events in specific organs of the body. Target organs are usually
identified based on adverse response of an organ to low exposure of a particular toxin.
Most common organs that are affected due to toxins are the respiratory system, nervous
system, skin, and the cardiovascular and hematologic system (Pereira et al., 2012).
Answer 4
Although the word toxin is most commonly interchangeable used with poison, and evokes a
sense of destruction or harm, these chemical compounds have been used since several centuries
as potential medicines and for other purpose as well. Some of the most common beneficial
applications of toxin are mentioned below:

6TOXICOLOGY
 Toxic ingredients derived from plant bark are used to inhibit cancers (Weaver, 2014)
 Some natural toxins are also used for numbing surgery pain (Jackson, Kuriyama &
Hayashino, 2012)
 Poisonous extracts have been used as cough remedies since centuries
 Animal toxins are used in the form of anticoagulants (Kaiser et al., 2012)
 Synthetic version of animal drugs are used to lower blood glucose levels and treat
hypertension (Buse et al., 2013)
 Plant toxins such as nicotine and caffeine are used to produce pleasurable effects (Sharma
et al., 2015)
Tetrodotoxin- This is a potent neurotoxin that is produced by pufferfish, sunfish and
triggerfish. It is a thermostable and water soluble non-protein that blocks sodium diffusion
through sodium channels, thereby preventing depolarisaton. This prevents action potential
transmission across neurons, by acting on the CNS and the PNS. Upon entering the human body
through ingestion, injection, or inhalation, the toxin results in several symptoms such as,
headache, dysarthria, nausea, vomiting, dysphagia, diaphoresis and abdominal pain.
Furthermore, exposure to higher doses of the toxin most often results in paralysis of the
diaphragm, thereby resulting in death due to failure of the respiratory system (Chen & Chung,
2014). However, it has been applied in modern therapeutic research for managing chemotherapy
induced neuropathic pain. Use of tetrodotoxin has showed significant inhibition in the expression
of heat hyperalgesia, and cold and mechanical allodynia (Qiu et al., 2012). Furthermore, research
findings also indicated that changes in gene regulation upon administration of this toxin results in
electrophysiological changes that plays a major role in outcome of pain pathogenesis. Altered

7TOXICOLOGY
changes in expression of tetrodotoxin sensitive VGSCs signify its effectiveness in treating
neuropathic pain (Nieto et al., 2012).

8TOXICOLOGY
References
Alomar, M. J. (2014). Factors affecting the development of adverse drug reactions. Saudi
Pharmaceutical Journal, 22(2), 83-94.
Anfossi, L., Baggiani, C., Giovannoli, C., D’Arco, G., & Giraudi, G. (2013). Lateral-flow
immunoassays for mycotoxins and phycotoxins: a review. Analytical and bioanalytical
chemistry, 405(2-3), 467-480.
Buse, J. B., Nauck, M., Forst, T., Sheu, W. H., Shenouda, S. K., Heilmann, C. R., ... & Porter, L.
(2013). Exenatide once weekly versus liraglutide once daily in patients with type 2
diabetes (DURATION-6): a randomised, open-label study. The Lancet, 381(9861), 117-
124.
Chen, R., & Chung, S. H. (2014). Mechanism of tetrodotoxin block and resistance in sodium
channels. Biochemical and biophysical research communications, 446(1), 370-374.
DeWitt, J. C., Peden-Adams, M. M., Keller, J. M., & Germolec, D. R. (2012). Immunotoxicity of
perfluorinated compounds: recent developments. Toxicologic pathology, 40(2), 300-311.
Greaney, A. J., Leppla, S. H., & Moayeri, M. (2015). Bacterial exotoxins and the
inflammasome. Frontiers in immunology, 6, 570.
Ibanez, S., Gallet, C., & Després, L. (2012). Plant insecticidal toxins in ecological
networks. Toxins, 4(4), 228-243.
Iwasaki, A., & Medzhitov, R. (2015). Control of adaptive immunity by the innate immune
system. Nature immunology, 16(4), 343.

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Jackson, J. L., Kuriyama, A., & Hayashino, Y. (2012). Botulinum toxin A for prophylactic
treatment of migraine and tension headaches in adults: a meta-analysis. Jama, 307(16),
1736-1745.
Jaishankar, M., Tseten, T., Anbalagan, N., Mathew, B. B., & Beeregowda, K. N. (2014).
Toxicity, mechanism and health effects of some heavy metals. Interdisciplinary
toxicology, 7(2), 60-72.0
Kaiser, A. F. C., Neubauer, H., Franken, C. C., Krüger, J. C., Mügge, A., & Meves, S. H. (2012).
Which is the best anticoagulant for whole blood aggregometry platelet function testing?
Comparison of six anticoagulants and diverse storage conditions. Platelets, 23(5), 359-
367.
Kalia, J., Milescu, M., Salvatierra, J., Wagner, J., Klint, J. K., King, G. F., ... & Bosmans, F.
(2015). From foe to friend: using animal toxins to investigate ion channel
function. Journal of molecular biology, 427(1), 158-175.
Llop, S., Lopez-Espinosa, M. J., Rebagliato, M., & Ballester, F. (2013). Gender differences in
the neurotoxicity of metals in children. Toxicology, 311(1-2), 3-12.
Magdolenova, Z., Collins, A., Kumar, A., Dhawan, A., Stone, V., & Dusinska, M. (2014).
Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered
nanoparticles. Nanotoxicology, 8(3), 233-278.
Meseguer, V., Alpizar, Y. A., Luis, E., Tajada, S., Denlinger, B., Fajardo, O., ... & Navia, B.
(2014). TRPA1 channels mediate acute neurogenic inflammation and pain produced by
bacterial endotoxins. Nature communications, 5, 3125.

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Nieto, F. R., Cobos, E. J., Tejada, M. Á., Sánchez-Fernández, C., González-Cano, R., & Cendán,
C. M. (2012). Tetrodotoxin (TTX) as a therapeutic agent for pain. Marine drugs, 10(2),
281-305.
Pereira, C. V., Nadanaciva, S., Oliveira, P. J., & Will, Y. (2012). The contribution of oxidative
stress to drug-induced organ toxicity and its detection in vitro and in vivo. Expert opinion
on drug metabolism & toxicology, 8(2), 219-237.
Qiu, F., Jiang, Y., Zhang, H., Liu, Y., & Mi, W. (2012). Increased expression of tetrodotoxin-
resistant sodium channels Nav1. 8 and Nav1. 9 within dorsal root ganglia in a rat model
of bone cancer pain. Neuroscience letters, 512(2), 61-66.
Sgambellone, M. A., David, A., Garner, R. N., Dunbar, K. R., & Turro, C. (2013). Cellular
toxicity induced by the photorelease of a caged bioactive molecule: design of a potential
dual-action Ru (II) complex. Journal of the American Chemical Society, 135(30), 11274-
11282.
Sharma, R., Lodhi, S., Sahota, P., & Thakkar, M. M. (2015). Nicotine administration in the
wake‐promoting basal forebrain attenuates sleep‐promoting effects of alcohol. Journal of
neurochemistry, 135(2), 323-331.
Sompayrac, L. M. (2015). How the immune system works. John Wiley & Sons, 117-126.
Weaver, B. A. (2014). How Taxol/paclitaxel kills cancer cells. Molecular biology of the
cell, 25(18), 2677-2681.