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OSH 5303-22.02.00-3B24-S2, Advanced ToxicologyUnit VIII JournalAssignment ContentImagine that you are the head of the Safety department at a facility that produces electronics and handles beryllium. You are responsible for preparing a training seminar presentation for a group of managers at your facility. This training needs to be in depth and detailed as the managers are required to have a thorough understanding of the materials to be able to properly oversee and prevent hazards in their individual areas.Prepare a PowerPoint presentation that discusses the following:
Discuss the absorption, distribution, metabolism, and excretion of beryllium.Common routes of exposure and effects of beryllium.Explain the bioaccumulation of metals as it affects ecology and humans.Be sure to summarize information in your own words as much as possible because the managers at your facility are not scientists. Utilize at least four visual aids that directly correlate to your discussion to clarify information. Visual aids may be in the form of pictures, flow charts, tables, or diagrams. Include a minimum of two credible sources.Your PowerPoint presentation should be at least seven slides in length and include speaker notes. The presentation will include a title and reference slide. The title and reference slides do not count toward the minimum requirement. All sources used will be properly cited and formatted in APA Style.
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UNIT VIII STUDY GUIDE
Absorption, Distribution,
Metabolism, and Excretion
Course Learning Outcomes for Unit VIII
At the end of this unit, you 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 molecular processes related to toxicity.
4.1 Investigate alterations in biotransformation and molecular targets that can be altered to result in
toxicity.
Required Unit Resources
Chapter 2: Xenobiotic Absorption, Distribution, Metabolism, and Excretion (ULO 3.1, 4.1)
Unit Lesson
Lesson (ULO 3.1, 4.1)
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 et al., 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 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
digestive tract through the stomach and down through the large and small intestines. The first pass effect, or
the way the compound is broken down by the digestive tract, will reduce the availability of the substance to
the body, and therefore, lower the degree of impact, depending on the specific characteristics of the chemical
or drug (Roberts et al., 2022). 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. Hogberg et al.(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
OSH 5303, Advanced Toxicology
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xenobiotic in the body. Water soluble, small, uncharged molecules, univalent cations,
and most
anions diffuse
UNIT x STUDY
GUIDE
easily and will eventually reach a relatively even distribution in the body. SomeTitle
xenobiotics, following the first
distribution phase, will be redistributed to tissue and can circulate in the system multiple times (Roberts et al.,
2022). 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., 2022).
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., 2022). 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 because of Phase I reactions and are able to be excreted
through the kidneys (Mycek et al., 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 glucuronide. 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 because 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., 2022). 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., 2022).
Exhalation is the only form of excretion that is effective for xenobiotics that are in the form of gases or highpressure 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,
causing alterations in function of the cells and the overall organ. Toxicity can also occur by inhibiting other
molecules from entering the cells, resulting in an abnormal extracellular accumulation 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., 2022). 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
OSH 5303, Advanced Toxicology
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produce immediate toxic effects, while others produce effects after the toxicantUNIT
has xbeen
absorbed
and
STUDY
GUIDE
distributed to other parts of the body. While toxicity is an inherent property of aTitle
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
Barton, H. A., Pastoor, T. P., Baetcke, K., Chambers, J. E., Diliberto, J., Doerrer, N. G., Driver, J. H.,
Hastings, C. E., Iyengar, S., Krieger, R., Stahl, B., & Timchalk, C. (2006). The acquisition and
application of absorption, distribution, metabolism, and excretion (ADME) data in agricultural chemical
safety assessments. Critical Reviews in Toxicology, 36(1), 9–35.
https://libraryresources.columbiasouthern.edu/login?url=https://search.ebscohost.com/login.aspx?dire
ct=true&db=asn&AN=19978303&site=eds-live&scope=site
Högberg, J., Holmberg, B., & Johanson, G. (2022, July 26). Definitions and concepts. In J. M. Stellman (Ed.),
Encyclopedia of occupational health and safety (4th ed.). International Labour Office.
https://www.iloencyclopaedia.org/part-iv-66769/toxicology-57951/general-principles-oftoxicology/item/4
Mycek, M. J., Harvey, R. A., & Champe, P. C. (1997). Pharmacology (2nd ed.). Lippincott-Raven.
Roberts, S. M., James, R. C., & Williams, P. L. (Eds.). (2022). Principles of toxicology: Environmental and
industrial applications (4th ed.). Wiley.
Suggested Unit Resources
In order to access the following resource, click the link below.
Article: The acquisition and application of absorption, distribution, metabolism, and excretion (ADME) data in
agricultural chemical safety assessments (Optional)
This article provides a good supplement to the Unit II assigned reading. It discusses how the four
cornerstones of toxicology are applied to safety assessments of pesticides.
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?
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