Advanced Toxicology

MOS 5425, Advanced Toxicology 1

Course Learning Outcomes for Unit V Upon completion of this unit, students should be able to:

6. Assess the effects of various toxicants on body systems. 6.1 Analyze research findings related to nephrotoxicity. 6.2 Relate scientific research findings to the field of safety.

Course/Unit Learning Outcomes

Learning Activity

6 Unit Lesson

6.1 Unit Lesson Chapter 7 Article Critique

6.2 Chapters 7 and 9 Article Critique

Reading Assignment Chapter 7: Nephrotoxicity: Toxic Responses of the Kidney, pp. 139-155 Chapter 9: Dermatotoxicity: Toxic Effects on the Skin, pp. 169-176

Unit Lesson This unit covers toxicology of the kidneys and skin. Although not discussed in the textbook, this lesson also includes a noteworthy discussion of the eye. Your reading begins with examining toxicology of the kidneys. If you have ever taken an anatomy course, you may recall that we have two kidneys that are each about the size of your fist, located near the base of the rib cage. The main function of the kidneys is to remove waste products from the body. This is a very important job because waste that is not removed and remains in the body can be potentially toxic. The kidneys are also involved in other important functions such as maintenance of the balance of certain electrolytes in the body, blood pressure regulation, vitamin D activation, and red blood cell production (National Kidney Foundation, n.d.). The kidneys are commonly known for their function of removing wastes from the body, but the kidneys also perform other important functions. Another function of the kidneys is to maintain homeostasis of various electrolytes such as potassium and sodium and to maintain proper levels of water within the body. The kidneys also possess specialized endocrine functions such as production of vitamin D and the protein erythropoietin (Roberts, James, & Williams, 2015). In additional, the kidneys are able to metabolize certain drugs. How do the kidneys remove waste from the body? This is done by the excretion of waste products in the urine. There are many terms that you will want to understand and identify when studying the kidneys. When discussing the production of urine and removal of waste from the body, you will need to focus your attention to the nephrons. Imagine the nephron as a long, continuous tube with varying diameters. This tube is bigger in some sections and smaller in other sections. In addition to the varying diameter, this tube has many bends and turns. Keeping this in mind, pay attention to the different names and specific functions of each area along this tube. Your textbook provides a diagram of the nephrons with each section labeled with the appropriate name. Take some time to look for other diagrams of nephrons on the Internet; doing so may provide a clearer overall understanding.

UNIT V STUDY GUIDE

Toxicology of the Kidneys, Skin, and Eyes

MOS 5425, Advanced Toxicology 2

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The kidneys function to remove wastes, drugs, and toxicants from the body through the excretion of urine. Different toxicants affect specific parts of the kidneys and ultimately can affect the proper functioning of the kidneys as organs. Many antibiotics are secreted by the proximal tubules and can induce alterations in the tubular functions and affect the overall function of the kidneys. In your textbook reading, note the different toxicants and the specific areas of the kidneys that they affect. Chemicals may cause acute as well as chronic injury to the kidneys. Various chemicals in the environment and industry as well as therapeutic drugs can induce nephrotoxicity. Halogenated solvents (e.g., dichloroethylene and perchloroethylene), heavy metals (e.g., mercury and cadmium), analgesics (e.g., acetaminophen, antibiotics), and antineoplastics (e.g., cisplatin) are all examples of chemicals that can induce nephrotoxicity (Roberts et al., 2015). The degree of damage that is induced depends not only on the type of chemical but the dose and duration of exposure to the chemical. The next section in your reading is about toxicology of the skin. The skin may be referred to as one of the largest organs of the body. The skin has several protective functions. It protects against water loss, slows chemical absorption, acts as a barrier for physical trauma, prevents ultraviolet (UV) light penetration and damage, inhibits microorganism growth and penetration, and helps to maintain homeostasis through regulation of body temperature and water loss (Roberts et al., 2015). It is the first line of defense in protecting our bodies from the invasion of harmful substances and toxicants. The skin serves as a barrier between external factors and the internal environment of our bodies. As a result, this barrier comes in contact with and encounters damage from a variety of substances as it serves to protect the body. Despite the skin being fairly thin compared to other organs of the body, it consists of three different layers: (1) the epidermis, (2) the dermis, and (3) the hypodermis. Your textbook discusses the first two layers. The epidermis is the outermost layer, and it is much thinner than the dermis. While reading the textbook, you should pay attention to the different cells that make up each of these layers and the role that each type of cell plays in the skin. Not only can toxicants damage the layers of skin, but they can also alter the hair, sebaceous glands, and sweat glands that span the epidermis and are embedded in the dermis (Roberts et al., 2015). The skin is a good barrier but not a perfect barrier against numerous substances. There are some substances that the skin is not able to shield from entering the body. Many factors influence the entrance or diffusion rate of chemicals across the skin (Roberts et al., 2015). The stratum corneum is the primary layer determining the rate of diffusion of chemicals through the skin. Due to the composition of the stratum corneum, small hydrophobic agents can more readily cross the skin barrier than molecules that are larger in size or molecules that are hydrophilic (Roberts et al., 2015). Certain conditions may compromise the skin’s ability to act as an effective barrier. One example is skin that has been exposed to water for an extended periods of time becomes more susceptible to hydrophilic substances passing through the skin’s surface. Toxicants can have different effects on the skin. Irritant dermatitis can occur on initial exposure; repeated exposure is not required becaise it is in contact dermatitis. Irritant dermatitis is limited to the local area of exposure and can include symptoms such as skin redness, blistering, eczema, and rashes (Roberts et al., 2015). Other types of dermal toxicity include allergic contact dermatitis, which is a hypersensitive reaction by the immune system following a repeat exposure to a chemical, and systemic contact dermatitis when a contact allergen enters an individual’s systemic circulation. Some of the symptoms of systemic contact dermatitis include headaches and malaise. Photosensitivity can be a result of dermal toxicity. It can be described simply as an extreme sensitivity to sunlight. Acneiform dermatoses, commonly referred to as acne, can be a response to dermal toxicity as a result of workplace exposures to petroleum, coal, and tar (Roberts et al., 2015). One of the last effects of dermal toxicity that the textbook mentions is the most common cancer in humans, skin cancer. UV exposure is the main cause of skin cancer, but chemical exposure to the skin may also induce skin cancer. The textbook does not include a discussion of the eye nor toxicity that may occur. However, the eyes are a vital part of the average person’s ability to function, so it is a noteworthy topic to address. The main function of the eye is for sight. The sense of sight serves an important role in protecting the body from harm. The eye has a complex anatomy with many intricate parts. You are encouraged to utilize your resources on the Internet to look at several detailed colored pictures and diagrams of the eye to get a good basic understanding of this structure. One question that may arise is how do we see objects? Light that is reflected off of objects travels

MOS 5425, Advanced Toxicology 3

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through many parts of the eye, including the cornea and aqueous humor all the way to the lens and retina. Signals that travel to the optic nerve are sent to the brain for interpretation to create the forms that we see.

Damage to any part of the structure of the eye can inhibit light from successfully traveling to the optic nerve and sending signals to the brain to interpret sight. Various chemicals may have different effects on various parts of the eyes. A brief search on corneal toxicity may reveal numerous chemicals that cause toxicity to the eye. Take note of how various chemicals affect different structures of the eye. There are several tests that can be performed to assess damage caused by exposure to various toxicants. Rabbits are the most common animal used in testing effects of chemicals on the eye. It is not uncommon for products that are sold in stores and are common household products used daily to be tested for the toxicological effects on the eye. One product that comes to mind is makeup. There is a high probability that in applying and wearing make-up people will at some point get make-up in their eyes. Consumers would like to believe that these products will not have adverse effects and, thus, are tested prior to being placed on the retail shelves to be sold. The tests performed to determine toxicity to the eye may

include, but are not limited to, procedures for gross anatomy testing, instrumental examinations using ophthalmoscopy, visual perimetry, and histological and biochemical examinations (Roberts et al., 2015).

References Clker-Free-Vector-Images. (2012). Eye diagram [Image]. Retrieved from https://pixabay.com/en/eye-diagram-

eyeball-body-pupil-39998/ National Kidney Foundation. (n.d.). How your kidneys work. Retrieved from

http://www.kidney.org/kidneydisease/howkidneyswrk.cfm#where Roberts, S. M., James, R. C., & Williams, P. L. (Eds.). (2015). Principles of toxicology: Environmental and

industrial applications (3rd ed.). Hoboken, NJ: Wiley.

Cross-section of the eye showing major components (Clker-Free-Vector-Images, 2012)