InstructionsPesticides are a common environmental concern due to the potential long-term effects of the chemicals and their metabolites on the immediate environment and ecosystem. For this assignment, research a common pesticide and write a three-page research paper that includes the following components:Identify the main active ingredient of the pesticide and how the pesticide is used.Identify and describe which of the four cornerstones of xenobiotic pharmacokinetics are affected in the way the pesticide works to kill the targeted organism.Identify the metabolites of the active ingredient of the pesticide, and discuss the toxicity and lifespan of the metabolites. Be sure to address the cornerstone processes associated with xenobiotic metabolism of the pesticide through the body.Provide your thoughts on whether or not this pesticide is safe for the overall ecosystem in the manner it is used and the resulting effects of its application as it breaks down into its metabolites. Can this biotransformation result in toxicity?The assignment should be completed as a text document and should meet the following requirements:The discussion should include the four aspects of the assignment as outlined above.The paper should be at least three pages in length, not including the title or reference page. Use proper APA formatting for all citations and references.A minimum of three credible references should be used for this assignment, and the references should be properly cited in the text as well as in a reference list.
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Instructions
Pesticides are a common environmental concern due to the potential long-term effects of the chemicals
and their metabolites on the immediate environment and ecosystem. For this assignment, research a
common pesticide and write a three-page research paper that includes the following components:
1. Identify the main active ingredient of the pesticide and how the pesticide is used.
2. Identify and describe which of the four cornerstones of xenobiotic pharmacokinetics are
affected in the way the pesticide works to kill the targeted organism.
3. Identify the metabolites of the active ingredient of the pesticide, and discuss the toxicity and
lifespan of the metabolites. Be sure to address the cornerstone processes associated with
xenobiotic metabolism of the pesticide through the body.
4. Provide your thoughts on whether or not this pesticide is safe for the overall ecosystem in the
manner it is used and the resulting effects of its application as it breaks down into its
metabolites. Can this biotransformation result in toxicity?
The assignment should be completed as a text document and should meet the following requirements:
1. The discussion should include the four aspects of the assignment as outlined above.
2. The paper should be at least three pages in length, not including the title or reference page. Use
proper APA formatting for all citations and references.
3. A minimum of three credible references should be used for this assignment, and the references
should be properly cited in the text as well as in a reference list.
UNIT II STUDY GUIDE
Absorption, Distribution, Metabolism, and Excretion
Course Learning Outcomes for Unit II
Upon completion of this unit, students should be able to:
3. Explain biological processes related to the processing of toxins in the body.
3.1 Summarize the cornerstone processes associated with xenobiotic metabolism through the
body.
4. Discuss cellular and molecular characteristics and processes related to toxicity.
4.1 Investigate alterations in biotransformation and molecular targets that can be altered to result in
toxicity.
Course/Unit
Learning Outcomes
3
3.1
4
4.1
Learning Activity
Unit Lesson
Chapter 2
Unit Lesson
Chapter 2
Research Paper
Unit Lesson
Chapter 2
Unit Lesson
Chapter 2
Research Paper
Reading Assignment
Chapter 2: Xenobiotic Absorption, Distribution, Metabolism, and Excretion, pp. 29-57.
Unit Lesson
Biological processes involved in metabolizing toxins and characteristics and processes associated with
toxicity must be addressed when discussing toxins and toxicity in the body. The textbook refers to absorption,
distribution, metabolism, and excretion as the four cornerstones of xenobiotic pharmacokinetics. These
processes are key to understanding how toxins, drugs, chemicals, or foreign molecules move through the
body, affect the systems of the body, and are disposed (Roberts, James, & Williams, 2015). Understanding
these concepts will lead to understanding how to avoid exposure to xenobiotics that can lead to possible
toxicity. As shown in the figure below, this process is necessary for the elimination of xenobiotics from the
body. The process of eliminating xenobiotics may involve the conversion to less toxic, and sometimes more
toxic, metabolites in the body.
Absorption
Distribution
Metabolism
Excretion
The four cornerstones of pharmacokinetics
Absorption is the first cornerstone. Absorption can also be considered as the various possible routes of
absorption of a chemical. When you think about protecting a child from toxic exposure to a chemical, you may
often think about preventing the digestion of a chemical or drug as children so often like to place things in
their mouths. This route of exposure can lead to absorption through the mouth (buccal cavity), followed by the
MOS 5425, Advanced Toxicology
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digestive tract through the stomach and down through the large and small intestines.
first GUIDE
pass effect, or
UNIT x The
STUDY
the way the compound is broken down by the digestive tract, will reduce the availability
of the substance to
Title
the body, and therefore, lower the degree of impact, depending on the specific characteristics of the chemical
or drug (Roberts et al., 2015). Another obvious point of exposure that can lead to absorption of a chemical is
when airborne particles or a gas is inhaled. Inhalation of a xenobiotic can lead to absorption through the
lungs. Another route of exposure that is often overlooked is exposure and absorption through the skin, the
largest organ of the body.
The next cornerstone is distribution. Following the entrance of a xenobiotic into the body, the chemical would
then be distributed throughout the system. Holmberg, Högberg, and Johanson (n.d.) state that distribution
depends on several factors that include the uptake and elimination rates, blood flow to various tissues, and
the affinity for the xenobiotic in the body. Water soluble, small, uncharged molecules, univalent cations, and
most anions diffuse easily and will eventually reach a relatively even distribution in the body. Some
xenobiotics, following the first distribution phase, will be redistributed to tissue and can circulate in the system
multiple times (Roberts et al., 2015). Xenobiotics may accumulate in fat or other areas, such as in the bone,
and become more concentrated as accumulation is extended and continues over time (Roberts et al., 2015).
Metabolism of a xenobiotic, the third cornerstone, is the breakdown or biotransformation of the compound into
a form that can be more readily excreted from the body. The goal of biotransformation is to create a molecule
that can be excreted from the body, but sometimes, the metabolite that is formed is more toxic to the body
than the original form. There are two sets of biotransformation reactions, simply referred to as Phase I and
Phase II reactions. Phase I reactions make the xenobiotics more water soluble. A water soluble molecule can
be excreted easily compared to a lipid soluble compound that will be attracted to fat in various tissues. The
Phase I reactions will often form highly reactive metabolites through oxidation of the compound (Roberts et
al., 2015). Some metabolites following Phase I reactions can be excreted from the body, while other Phase I
reactions will prepare other xenobiotics for Phase II reactions. Phase I reactions include oxidation, hydrolysis,
and reduction reactions. Xenobiotics will undergo conjugation during Phase II reactions to further increase the
water solubility of the compounds for excretion. Biotransformation can take place in multiple organs, but the
most prevalent is the liver because of the vast quantity of enzymes found in the liver to facilitate the reactions.
Once the xenobiotics have undergone biotransformation, then they are ready to be excreted from the body.
Some toxins may be converted to polar metabolites as a result of Phase I reactions and are able to be
excreted through the kidneys (Mycek, Harvey, & Champe, 1997). Metabolites that are retained in the body
may undergo Phase II (conjugation) reactions to further convert the metabolite to a form that can be excreted
from the body. Phase II reactions involve several types of endogenous metabolites such as glucocuronide.
Toxicants generally undergo several types of biotransformation that result in a variety of metabolites and
conjugates. Some chemicals may become toxic once they are metabolized and others can be broken down
into less toxic forms. Some can be metabolized through dealkylation, oxidation, desulfuration, or hydrolysis,
yielding 10 or more different metabolites. An individual’s age may also play a major factor in effectively
excreting chemicals from the body and, therefore, the severity of the toxic effects as a result of similar levels
of exposure to a substance may be vastly different depending on the age.
The last step is excretion. Excretion is the process of eliminating the xenobiotic from the body. Elimination can
occur through urine and bile by renal excretion through the kidneys and biliary excretion. Elimination may also
occur through the respiratory system from exhalation as well as through milk excretions. The most common
route of elimination is through renal excretion. This route of elimination most often excretes the metabolites of
Phase II conjugates (Roberts et al., 2015). Biliary excretion is when liver cells or hepatocytes remove the
xenobiotic from plasma and transform it into bile that enters the gastrointestinal tract and is excreted in the
stool. Sometimes, the xenobiotics that enter the liver can also reenter the bloodstream and become available
for renal excretion (Roberts et al., 2015). Exhalation is the only form of excretion that is effective for
xenobiotics that are in the form of gases or high pressure vapors. Due to the characteristics of milk, some
xenobiotics tend to accumulate and are excreted in the milk. This can be potentially dangerous and/or fatal for
a nursing infant who is obtaining milk from a mother who has been exposed to a xenobiotic—such as
morphine or alcohol—that will accumulate in the milk and be excreted to the nursing infant.
Alterations to the cellular level of an organism can affect the toxic ability of a chemical. The four mechanisms
by which a toxicant may pass through a cell membrane are passive diffusion, filtration through the membrane
pores, carrier-mediated transport, and endocytosis (engulfing by the cell). The ease of passage of a molecule
through the phospholipid membrane of a cell depends on several factors. These factors include the size,
charge, and/or ability to utilize a carrier protein for passage. Toxicity may occur as chemicals enter the cells,
MOS 5425, Advanced Toxicology
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causing alterations in function of the cells and the overall organ. Toxicity can also
by inhibiting
UNIToccur
x STUDY
GUIDEother
molecules from entering the cells, resulting in an abnormal extracellular accumulation
Title of the substance that
can result in toxicity. This can also deny the necessary molecules from entering the cell that will ultimately
inhibit the cell from performing normal functions (Roberts et al., 2015). Halting transport of molecules into or
out of cells can inhibit the excretion and elimination of a toxin, allowing an accumulation within the body, thus
affecting the organism at the cellular level.
The local effects of certain chemicals can be induced by caustic substances in the gastrointestinal tract, by
corrosive materials on the skin, and by irritant gases and vapors in the respiratory tract. Many toxicants
produce immediate toxic effects, while others produce effects after the toxicant has been absorbed and
distributed to other parts of the body. While toxicity is an inherent property of a substance, the nature and
extent of the toxic manifestations in an organism that is exposed to the substance depend on many factors.
These factors include the dose and duration of exposure; the species and strain of the animal; and the sex,
age, and nutritional/hormonal status of the animal. Various environmental (physical and social) factors also
play a part. In addition to the specific characteristics of the animal, the toxicant’s effects will also depend on its
interaction with other chemicals present. The toxicity of a chemical in an organism may be increased or
decreased by a simultaneous or consecutive exposure to another chemical.
References
Holmberg, B., Högberg, J., & Johanson, G. (n.d.). Toxicology. In Encyclopaedia of occupational health and
safety. Retrieved from http://www.ilocis.org/documents/chpt33e.htm
Mycek, M. J., Harvey, R. A., & Champe, P. C. (1997). Pharmacology (2nd ed.). Philadelphia, PA: LippincottRaven.
Roberts, S. M., James, R. C., & Williams, P. L. (Eds.). (2015). Principles of toxicology: Environmental and
industrial applications (3rd ed.). Hoboken, NJ: Wiley.
Suggested Reading
In order to access the following resource, click the link below.
This article provides a good supplement to the Unit II assigned reading. It reinforces the toxicology basics and
applies them to current research trends. In addition to the topics covered in the lesson, it introduces particle
size as an important factor in toxicology.
Grabinski, C. (2015). Toxicology 101. Chemical Engineering Progress, 111(11), 31-36. Retrieved from
https://libraryresources.columbiasouthern.edu/login?auth=CAS&url=http://search.proquest.com.library
resources.columbiasouthern.edu/docview/1733896512?accountid=33337
Learning Activities (Nongraded)
Nongraded Learning Activities are provided to aid students in their course of study. You do not have to submit
them. If you have questions, contact your instructor for further guidance and information.
Here are a few questions to consider as you complete the unit:
1. How does the solubility of the xenobiotic affect the absorption, distribution, metabolism, and excretion
(ADME) of the molecule?
2. What are the main events of Phase I and Phase II reactions?
3. What is the main goal of biotransformation?
4. How can the rate of metabolism affect toxicity?
MOS 5425, Advanced Toxicology
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