Kinetic And Nonkinetic Toxicology
Nonkinetic toxicology deals with generalized harmful effects of chemicals that occur at an exposure site a typical example is the destruction of skin tissue by contact with concentrated nitric acid, HNO3. Nonkinetic toxicology applies to those poisons that are not metabolized or transported in the body or subject to elimination processes that remove them from the body. The severity of a nonkinetic insult depends on both the characteristic of the chemical and the exposure site. Injury increases...
Diazotized Nitroaniline
Therefore, exposure to benzene can be determined by analysis of urine for phenol. Although a very sensitive colorimetric method for phenol involving diazotized p-nitroaniline has long been available, gas chromatographic analysis is now favored. The urine sample is treated with perchloric acid to hydrolyze phenol conjugates, and the phenol is extracted into diisopropyl ether for chromatographic analysis. Two other metabolic products of benzene, trans,trans-muconic acid8 and S-phenyl mer-capturic...
Reproductive System
Humans reproduce sexually to produce young that are born live. Sexual reproduction occurs when two gametes, sperm from males and eggs from females, each carrying a single set of chromosomes, unite in a process called fertilization. The fertilized egg, called a zygote, contains two sets of chromosomes, one from each of the gametes. The zygote begins the process of division and cell differentiation that results in an individual capable of living outside the womb at birth. The whole process is...
Reproductive And Developmental Effects
Some of the more serious effects of toxic substances are those that affect the reproduction of organisms and their development to adulthood.4 Because of the serious nature of these effects, they are commonly examined in animal studies of pharmaceuticals, pesticides, and other chemicals. Developmental toxic effects are those that adversely influence the growth and development of an organism to adulthood. These may occur from exposure of either parent of the organism to toxic substances even...
Hccccccch
H H H H H H H Valproic acid, 2-propylpentanoic acid Other than ethanol, the xenobiotic chemical best known to cause steatosis is carbon tetrachloride, CCl4. This compound was once widely used in industry as a solvent, and even in consumer items as a stain remover. As discussed in some detail in Chapter 16, it is converted by enzymatic action in the liver to Cl3C- radical, then by reaction with O2 to Cl3COO- radical, which reacts with unsaturated lipids in the liver to cause fatty liver. The...
Mixed Organometallic Compounds
So far in this chapter the discussion has centered on compounds in which all of the metal bonds are with carbon. A large number of compounds exist that have at least one bond between the metal and a C atom on an organic group, as well as other covalent or ionic bonds between the metal and atoms other than carbon. Because they have at least one metal-carbon bond, as well as properties, uses, and toxicological effects typical of organometallic compounds, it is useful to consider such compounds...
Examples of Endogenous Substances
Examples of endogenous substances in organisms include various hormones, glucose (blood sugar), some vitamins, and some essential metal ions, including Ca2+, K+, and Na+. Calcium in human blood serum exhibits the kind of behavior shown in Figure 6.8, with an optimum level that occurs over a rather narrow range of 9 to 9.5 mg dL. Below these values, a toxic response known as hypocalcemia occurs, manifested by muscle cramping. At serum levels above about 10.5 mg dL, hypercalcemia occurs, the...
H H H
Another even more widely used pharmaceutical that has been linked indirectly to numerous deaths is sildenafil citrate, marketed as the impotence drug Viagra. Used by millions during the few years since it was introduced, numerous deaths have been reported among men taking the drug along with nitroglycerin or nitrates administered for the treatment of heart disease. It is believed that the combination of these drugs with Viagra reduce blood flow through damaged coronary arteries, causing fatal...
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Phototoxic responses of skin occur as the result of absorption of radiation, primarily sunlight and ultraviolet radiation in the UVB region of 290 to 320 nm. Because UVB radiation is vastly more effective in causing phototoxic symptoms than either UVA radiation (320 to 400 nm) or visible light (400 to 700 nm), reference will be made to it in discussions of phototoxicity. Photons of radiation are absorbed by functional groups called chromophores on biomolecules. The most significant chromophores...
Skin
The pulmonary system and skin constitute the major routes of entry for xenobiotic materials into the body. The skin has a large surface area of up to two m2 for adults. This large area, along with skin's external exposure, means that it is a common site of contact with toxic substances, especially in the workplace. It has been estimated that about one third of all reported occupational exposures to toxic substances is through skin, and much larger numbers that produce relatively minor symptoms...
Vital Signs
Human subjects suffering from acute poisoning usually show alterations in the vital signs, which consist of temperature, pulse rate, respiratory rate, and blood pressure. These are discussed here in connection with their uses as indicators of toxicant exposure. Some toxicants that affect body temperature are shown in Figure 6.11. Among those that increase body temperature are benzadrine, cocaine, sodium fluoroacetate, tricyclic antidepressants, hexachlorobenzene, and salicylates (aspirin). In...
Respiratory System
In discussing toxic responses of the respiratory system, it is important to make a distinction between the respiratory system as an entryway for toxic substances, referred to as inhalation toxicology, and the respiratory system adversely affected by toxicants, referred to as respiratory tract toxicology. The term pulmonary refers to lungs. Generally, toxicants that adversely affect the respiratory system are those that have been inhaled, including such well-known substances as asbestos,...
H2n H h hch H
This substance reacts with oxidant radicals to produce H2O and the oxidized form of glutathione, consisting of two of the molecules of this substance joined by an SS bridge. A potent oxidizing form of elemental oxygen is ozone, O3. This species is arguably the most toxic environmental pollutant to which the general population is exposed because of its presence in polluted atmospheres, especially under conditions where photochemical smog is present. It can be a pollutant of the workplace in...
Toxification And Detoxification
As shown for the kinetic phase in Figure 6.10, a xenobiotic substance may be (1) detoxified by metabolic processes and eliminated from the body, (2) made more toxic (toxified) by metabolic processes and distributed to receptors, or (3) passed on to receptors as a metabolically unmodified toxicant. A metabolically unmodified toxicant is called an active parent compound, and a substance modified by metabolic processes is an active metabolite. Both types of species may be involved in the dynamic...
Inorganic Compounds Of Silicon
Because of its use in semiconductors, silicon has emerged as a key element in modern technology. Concurrent with this phenomenon has been an awareness of the toxicity of silicon compounds, many of which, fortunately, have relatively low toxicities. This section covers the toxico-logical aspects of inorganic silicon compounds. The silicon compound that has probably caused the most illness in humans is silica, SiO2. Silica is a hard mineral substance known as quartz in the pure form and occurring...
Genetic Susceptibilities And Resistance To Toxicants
The discussion in this chapter so far has focused on the toxicological implications of damage to DNA by toxic agents. However, the genetic implications of toxicology are much broader than damage to DNA because of the strong influence of genetic makeup on susceptibility and resistance to toxicants. It is known that susceptibility to certain kinds of cancers is influenced by genetic makeup. In Section 8.2, mention was made of oncogenes, associated with the development of cancer, and tumor...
Questions And Problems
Distinguish between acute toxicity and chronic toxicity. 2. Distinguish among acute local exposure, chronic local exposure, acute systemic exposure, and chronic systemic exposure to toxicants. 3. List and discuss the major routes and sites of exposure, distribution, and elimination of toxicants in the body. 4. What function is served by the stratum corneum in exposure of the body to toxic substances 5. Explain why the lungs are regarded as the place where substances external to the body have...
Nn
Figure 9.3 The iron-containing heme group on hemoglobin that binds with molecular oxygen and enables red blood cells to carry oxygen to tissues. Blood plasma is a straw-colored liquid laden with a variety of salts, nutrients, dissolved gases, and biomolecules, especially proteins. The major ionic component of blood is sodium chloride as Na+ and Cl- ions. Nutrients that circulate in blood include glucose (blood sugar), various amino acids, lipids, lactic acid, and cholesterol. An important...
Toxic Substances From Bacteria
Bacteria are sources of a number of toxic substances, including botulinus toxin, which is arguably the most deadly substance known.2 The two greatest concerns regarding toxic substances from bacteria are their roles in causing symptoms of bacterial disease and food poisoning. It is useful to consider as one class those bacteria that produce toxins that adversely affect a host in which the bacteria are growing, and as another class those bacteria that produce toxins to which another organism is...
Botulinum Toxin H Chemical Formula
It consists of four hydrogen atoms covalently bonded to a single nitrogen (N) atom, and it has a net electrical charge of +1 for the whole cation, as shown by its Lewis formula above. The transfer of two electrons from yields an ion of Mg2+ and one of an atom of Mg to an O atom O2- in the compound MgO. Formation of ionic MgO as shown by Lewis formulas and symbols. In MgO, Mg has lost 2 electrons and is in the +2 oxidation state Mg(II) and O has gained 2 electrons and is in the -2 oxidation...
The Liver
The liver is often the organ that is damaged by such chemicals and their metabolites. Recall from Chapter 8 that the livers of genetically susceptible individuals can be damaged by therapeutic doses of some drugs, such as those shown in Figure 8.5. Other xenobiotics ingested accidentally can damage the liver. Toxic effects to the liver are studied under the topic of hepatotoxicity, and substances that are toxic to the liver are called hepatotoxins. Much is known about hepatotoxicity from the...
The Anthrosphere And Green Chemistry
The anthrosphere is intimately entwined with the other environmental spheres examples of its interactions with these spheres abound. Arguably the greatest effect of the anthrosphere to date has been through the cultivation of vast areas of the geosphere to produce food for humans and their domesticated animals. Humans have drastically altered the hydrosphere, putting dams on rivers and otherwise altering their normal flow. Vast stores of water left over from the Ice Age in underground aquifers...
Specialized Areas of Toxicology
Given the huge variety of toxic substances and their toxic effects, it is obvious that toxicology is a large and diverse area. Three specialized areas of toxicology should be pointed out. Clinical toxicology is practiced primarily by physicians who look at the connection between toxic substances and the illnesses associated with them. For example, a clinical toxicologist would be involved in diagnosing and treating cases of poisoning. Forensic toxicology deals largely with the interface between...
