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Toxicology A Case-Oriented Approach - part 6 pdf

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© 2002 by CRC Press LLC TOXICITY OF SULFIDES Hydrogen sulfide has two major toxic actions. The first is a depressant effect on the CNS. A result of this effect is paralysis of the respiratory center and death. The second is inhibition of cytochrome oxidase in a manner very similar to the effect of cyanide. H 2 S is actually a more potent inhibitor of cytochrome oxidase than is cyanide. Carbon disulfide has some toxic features in common with H 2 S. It attacks the CNS and the cardiovascular system. However, it has its own uniquely toxic character in causing a peripheral neuropathy with cranial nerve damage (see Chapter 10 on neurotoxins). Curiously, it is also atherogenic in experimental animals. THERAPY The cyanide antidote kit is effective with H 2 S poisoning. The nitrites within the kit convert hemoglobin to methemoglobin which becomes an agent for binding hydro - gen sulfide before it can bind cytochrome oxidase and cause death. Sulfmethemo- globin is formed by the reaction between methemoglobin and either H 2 S or hydrogen sulfide anion and this substance is excreted into the urine as such or as nontoxic metabolites. LABORATORY TESTING Hydrogen sulfide is like cyanide in the sense that many victims will die too soon for laboratory evaluation to be of any help. However, testing for sulfide ion in blood may help to make the diagnosis for those who are less disabled. An ion-selective electrode has been developed for measurement of sulfide ion. Because this electrode is not completely specific to sulfide to the exclusion of all other ions, it is necessary to pre-treat the specimen and isolate sulfide. This has been done, in one method, with Conway microdiffusion cells. Concentrations of sulfide ion found in H 2 S deaths ranged from 1.7 to 3.75 µg/mL. HYDROCARBONS By definition these are compounds which contain only carbon and hydrogen. Many such compounds have been identified in the natural world, a good number of which are found in crude oil. They include the aliphatic alkanes, alkenes, and alkynes, which differ among each other in regard to the saturation of the carbon atoms. The most common members of this class are methane, ethane, propane, and butane. All members of this category are very abundant in the industrial world. The aromatic hydrocarbons include benzene and the many compounds derived from benzene. Halogenated hydrocarbons and organohalide insecticides are similar to hydro- carbons in some chemical and toxicological properties; however, they also have unique toxicological traits and will be discussed in a separate section of this text. © 2002 by CRC Press LLC TOXICITY OF SULFIDES Hydrogen sulfide has two major toxic actions. The first is a depressant effect on the CNS. A result of this effect is paralysis of the respiratory center and death. The second is inhibition of cytochrome oxidase in a manner very similar to the effect of cyanide. H 2 S is actually a more potent inhibitor of cytochrome oxidase than is cyanide. Carbon disulfide has some toxic features in common with H 2 S. It attacks the CNS and the cardiovascular system. However, it has its own uniquely toxic character in causing a peripheral neuropathy with cranial nerve damage (see Chapter 10 on neurotoxins). Curiously, it is also atherogenic in experimental animals. THERAPY The cyanide antidote kit is effective with H 2 S poisoning. The nitrites within the kit convert hemoglobin to methemoglobin which becomes an agent for binding hydro - gen sulfide before it can bind cytochrome oxidase and cause death. Sulfmethemo- globin is formed by the reaction between methemoglobin and either H 2 S or hydrogen sulfide anion and this substance is excreted into the urine as such or as nontoxic metabolites. LABORATORY TESTING Hydrogen sulfide is like cyanide in the sense that many victims will die too soon for laboratory evaluation to be of any help. However, testing for sulfide ion in blood may help to make the diagnosis for those who are less disabled. An ion-selective electrode has been developed for measurement of sulfide ion. Because this electrode is not completely specific to sulfide to the exclusion of all other ions, it is necessary to pre-treat the specimen and isolate sulfide. This has been done, in one method, with Conway microdiffusion cells. Concentrations of sulfide ion found in H 2 S deaths ranged from 1.7 to 3.75 µg/mL. HYDROCARBONS By definition these are compounds which contain only carbon and hydrogen. Many such compounds have been identified in the natural world, a good number of which are found in crude oil. They include the aliphatic alkanes, alkenes, and alkynes, which differ among each other in regard to the saturation of the carbon atoms. The most common members of this class are methane, ethane, propane, and butane. All members of this category are very abundant in the industrial world. The aromatic hydrocarbons include benzene and the many compounds derived from benzene. Halogenated hydrocarbons and organohalide insecticides are similar to hydro- carbons in some chemical and toxicological properties; however, they also have unique toxicological traits and will be discussed in a separate section of this text. © 2002 by CRC Press LLC Insecticides CONTENTS Organochlorine Insecticides Chemistry Benzene Hexachloride (Hexachlorocyclohexane) Cyclodienes Cage Structures Symptoms of Organochlorine Poisoning Therapy Organophosphate Insecticides Chemistry Physiology of Cholinergic Activity Characteristics of Organophosphate Poisoning Therapy Laboratory Testing Carbamates Pyrethrins Questions and Problems Insecticides are very beneficial to mankind because they help to control vector-borne diseases such as malaria, improve agricultural productivity, and reduce the angst which many forms of insects visit upon “picnicking man.” Ideally, they should be entirely species-specific or, at least, specific to invertebrates. This is, of course, not the case. Some insecticides are much more lethal to insects than to higher forms of life. Nonetheless, because they are harmful to all forms of life, at least to some degree, exposure to them can be fatal and they must be discussed in texts on toxicology. ORGANOCHLORINE INSECTICIDES The chlorinated hydrocarbon group of insecticides is large and includes what is possibly the most controversial compound of the twentieth century, DDT, dichlo - rodiphenyltrichloroethane (Figure 17.1). It was synthesized 125 years ago in 1874 but its ability to eliminate insect pests was not recognized until 1939. That recog- nition led to the 1948 Nobel prize for the responsible scientist, Dr. Paul Mueller, a Swiss chemist. Mueller discovered the potency of DDT while screening for insec - ticides for the JR Geigy Company. 17 © 2002 by CRC Press LLC Metals CONTENTS Arsenic History Forms of Arsenic Sources of Arsenic Mechanism of Arsenic Toxicity Symptoms of Arsenic Poisoning Treatment Chelators Chelating Agents for Use with Arsenic Poisoning Testing for Arsenic Lead History Sources of Lead Pharmacokinetics of Lead Mechanism of Toxicity Symptoms of Lead Poisoning Treatment of Lead Intoxication The Laboratory and Lead Overdose Mercury History Types and Sources of Mercury Toxicokinetics of Mercury Signs of Mercury Poisoning Treatment of Mercury Poisoning Laboratory Testing and Mercury Iron Toxicokinetics Iron Toxicity Treatment Deferoxamine (Deferoxamine Mesylate, Desferal) Laboratory Involvement Laboratory Testing Methods Questions and Problems Further Reading 18 . with H 2 S. It attacks the CNS and the cardiovascular system. However, it has its own uniquely toxic character in causing a peripheral neuropathy with cranial nerve damage (see Chapter 10 on. with H 2 S. It attacks the CNS and the cardiovascular system. However, it has its own uniquely toxic character in causing a peripheral neuropathy with cranial nerve damage (see Chapter 10 on. of this category are very abundant in the industrial world. The aromatic hydrocarbons include benzene and the many compounds derived from benzene. Halogenated hydrocarbons and organohalide insecticides

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