Environmental Toxicology Paper

ENV/410
Environmental Toxicology Paper I will first explain the difference between toxicokinetics and toxicodynamics. Toxicants interact with living organisms in a series of five time-dependent processes. The study of these processes is called toxicokinetics. These processes are absorption, distribution storage, biotransformation and elimination. There are unique cellular effects within the organism when they come in contact with the toxicant. Toxicodynamics is an examination of the way these effects happen. There are many similarities as well as important differences between the toxicokinetics and pharmacokinetics of most substances. The same applies to pharmacodynamics and toxicodynamics (Olson, n.d.).
The approach for conducting toxicokinetics studies that is recommended by most scholars generally involves three steps. Goehl (1997), "Step 1 is a preliminary study, which uses a minimum number of animals to estimate the range of blood/tissue concentrations, the required quantitation limit for the analytical method, and the optimal sampling times for the definitive toxicokinetic studies. Step 2 is the definitive study and generates blood and/or tissue concentration data for calculating the toxicokinetic parameters. Step 3 is the toxicokinetic study conducted in conjunction with the toxicology study to determine the internal dose and the effects of age and continuous exposure on kinetic parameters” (Toxicokinetics in the National Toxicology Program).
There are four primary routes of exposure to chemical contaminants; injection, ingestion, topical and inhalation. Because of the chemical being directly introduced into the body, injection is the only method where the entire amount is absorbed regardless of how much is given. Chemicals may be injected intravenously directly into a vein or intramuscularly. The other methods of injection are subcutaneously, which is under the skin or intraperitoneally, directly into the membrane lining the organs of the stomach (Al-hamad, 2012).
Ingestion is the route of exposure most often used for toxic chemicals. The cell membrane diffuses chemicals in the non-ionized form, making the level of ionization important in whether a chemical is absorbed or not. Al-hamad (2012), "Organic acids are in their non- ionized form in an acidic environment (such as the stomach), and they thus tend to diffuse across a membrane, whereas organic bases are non-ionized and thus diffuse across a membrane in a basic environment (such as in the intestine)” (Different route of exposure of toxicant). Because the small intestine is larger than the stomach, its contents are passed to the intestine before the chemicals are absorbed (Al-hamad, 2012).
Topical exposure happens when the toxicant is absorbed through the skin. The absorption of the toxicant is directly proportional with the chemical’s lipid solubility. The thickness of the layer, the condition, the dryness and the state of the molecules are all factors that affect the rate of absorption through the skin (Al-hamad, 2012). Inhalation of toxic substances is the fourth way a toxic substance can enter the body. This can come in the form of gases or aerosols. Gas molecules tend to move into the blood through partitioning. The particle size and water solubility of aerosols will affect the rate of absorption through the lungs. (Al-hamad, 2012).
A chemical is absorbed into the interstitial fluid of an organ when it passes through the cell linings of the organ in question. Interstitial fluid makes up about 15% of our body weight. The intracellular fluid makes up about 40% of body weight with blood plasma accounting for about 8%. Instead of being isolated, these body fluids represent one large pool. Yuill (2010), "The interstitial and intracellular fluids remain in place with certain components moving slowly into and out of cells” (Distribution of toxicants in the body). While immersed in the interstitial fluid, a chemical is not mechanically transported as it is in blood. A toxicant can leave the interstitial fluid by various ways such as entering the lymphatic system, entering local tissue cells or entering blood capillaries and the blood circulatory system (Yuill, 2010).
There are four principal mechanisms in moving toxicants across the cell membrane. The first is called passive diffusion. There is a difference in concentration of the chemical between the outside of the cell and the inside. The more difference there is in this concentration, the greater chance there is of the chemical diffusing to the inside of the cell. Facilitated diffusion happens when carrier proteins transport water soluble chemicals across the membrane. The chemicals are, once again, moving from a higher concentration to a lower concentration. Active transport is when a chemical is moving against a concentration gradient. A membrane pump is such as the sodium/potassium ATPase pump is needed to transport potassium into the cell and sodium ions out. An active transport such as energy is required. Another mechanism is called endocytosis. The molecular weight of the chemical and the size of the pore determine whether diffusion takes place. The membrane engulfs the chemical, forming a vesicle, transporting it across the membrane (Zedeck, 2004).
One of the ways biotransformation is categorized is how they tend to react with a xenobiotic. These are called Phase I and Phase II reactions. Phase I works by adding a functional structure, thus modifying the chemical. The substance then fits into the Phase II enzyme, becoming joined together with another substance. Enzymatic reactions that join the modified xenobiotic with another substance are called a Phase II reaction. The molecules of the conjugated products are now larger than the substrate and water-soluble in nature (Monosson, 2012).
Monosson (2012), "Biotransformation is vital to survival in that it transforms absorbed nutrients (food, oxygen, etc.) into substances required for normal body functions” (Biotransformation). Biotransformation is vital to survival in that it transforms absorbed nutrients (food, oxygen, etc.) into substances required for normal body functions. For some pharmaceuticals, it is not the absorbed drug, but the metabolite that is therapeutic. Biotransformation is also an important defense mechanism, causing body wastes and toxic xenobiotics to be transformed into less harmful substances that can be excreted from the body (Monosson, 2012).
The environmental effect of toxicants is many and varied. Some of them can be a lower numbers of ovarian follicles in newborn eggs, the decay and death of sperm cells happening at an increased rate and females reaching puberty earlier. Other risks are cancer, impaired fetal brain development, Parkinson's disease, miscarriage, nerve damage, birth defects, blocking the absorption of food nutrients, heart disease, asthma, multiple sclerosis and diabetes.
One of the more toxic substances is mercury. According to "Jefferson Lab" (n.d.), "Mercury is not usually found free in nature and is primarily obtained from the mineral cinnabar (HgS)” (The Element Mercury). Mercury’s physical properties are: atomic mass average: 200.59, boiling point: 357oC / 675oF / 630K, electrical conductivity: 0.0104 X 106 / cm Ohm, thermal conductivity: 0.0834 W / cmK, density: 13.546 g / cm3 @ 300K, melting point: -38.72oC / -37.7oF / 234.28K, molar volume: 14.81 cm3 / mole, vapor pressure: 0.0002Pa @ -38.72oC and heat of vaporization: 59.229 kJ / mol. Mercury is poisonous and the respiratory tract, the digestive tract or directly through the skin are common entry ways into the body. One of the ways mercury crosses the cell wall or membrane mercury get into cells is with the help of the chemical sulfide. This is how it is thought to be able to cross the membrane of fish. Winner (2010), "Most forms of mercury can’t pass through a cell membrane because they are bound to large molecules or because they carry a charge” (How Does Toxic Mercury Get into Fish?). But when positively charged mercury ions meets negatively charged sulfide, the two bond. The resulting compound, HgS, is small and uncharged, which is able to pass into microbial cells (Winner, 2010).

References
Olson, K. R. (n.d.). Access pharmacy. Retrieved from http://accesspharmacy.mhmedical.com/content.aspx?bookid=388&sectionid=45764285&jumpsectionID=45774383
Goehl, T.J. (1997). PubMed.gov. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/9260193
Al-hamad, A. (2012). Slideshare. Retrieved from http://www.slideshare.net/AngelAlhamad/different-route-of-exposure-of-toxica
Yuill, T. (2010). The encyclopedia of earth. Retrieved from http://www.eoearth.org/view/article/151754/
Zedeck, M. (2004). Visionlearning. Retrieved from http://www.visionlearning.com/en/library/Biology/2/Absorption-Distribution-and-Storage-of-Chemicals/106
Monosson, E. (2012). The encyclopedia of earth. Retrieved from http://www.eoearth.org/view/article/150674/
Jefferson lab. (n.d.). Retrieved from http://education.jlab.org/itselemental/ele080.html
Winner, C. (2010). Oceanus magazine. Retrieved from https://www.whoi.edu/oceanus/feature/how-does-toxic-mercury-get-into-fish