Halogenated hydrocarbons metabolism

Guzelian PS, Mutter L, Fariss M, et al. 1981. Metabolism and biliary excretion of chlordecone (Kepone) in humans Toxicolology of halogenated hydrocarbons. Health and Ecological Effects. 1 315- 325. 

Brittebo EB, Eriksson C, Brandt I. 1990. Metabolic activation of halogenated hydrocarbons in the conjunctival epithelium and excretory ducts of the intraorbital lacrimal gland in mice. New York, NY Academic Press 245- 252. 

Unlike enflurane, isoflurane does not produce a seizurelike EEG pattern. Furthermore, the metabolic transformation of isoflurane is only one-tenth that of enflurane, so fluoride production is quite low. Among the halogenated hydrocarbons, isoflurane is one of the most popular, since it preserves cardiovascular stability and causes a low incidence of untoward effects. 

Halogenated Hydrocarbons. Halogenated hydrocarbons are not easily metabolized and show significant stability in vivo. The addition of halogens tends to increase the lipophilicity and to prolong the half-life of the drug. 

Brandt, 1. (1986) Metabolism-related tissue-binding of halogenated hydrocarbons. Uppsala J. med. Sci., 91, 289-294... 

A number of industrial chemicals have been linked to cardiotoxicity. Aldehydes and primary alcohols that can be metabolically oxidized to aldehydes have exhibited cardiodepressant effects. Acute exposure to ethanol has caused arrhythmia. Isopropyl alcohol (2-propanol), a widely used industrial chemical and personal care product, may cause cardiovascular depression and excessively rapid heartbeat. Some halogenated hydrocarbons, including chloroform, ethyl bromide, and trichlo-rofluoromethane, have been implicated in cardiovascular disorders, including arrhythmia. 

Postoperatively, the anesthesiologist withdraws the anesthetic mixture and monitors the immediate return of the patient to consciousness. For most anesthetic agents, recovery is the reverse of induction that is, redistribution from the site of action rather than metabolism underlies recovery. The anesthesiologist continues to monitor the patient to be sure that there are no delayed toxic reactions, for example, diffusion hypoxia for nitrous oxide, and hepato-toxicity with halogenated hydrocarbons. 

Riccio E, Griffin A, Mortelmans K, et al. 1983. A comparative mutagenicity study of volatile halogenated hydrocarbons using different metabolic activation systems. Environ Mut 5 472. 

Welch RM, Levin W, Kuntzman R, et al. 1971. Effect of halogenated hydrocarbon insecticides on the metabolism and uterotropic action on estrogens in rats and mice. Toxicol AppI Pharmacol 19 234-246. 

Inhalation at higher concentration causes CNS depression. Vapor/liquid contact will irritate eyes, nose, throat, and skin. Ketones may potentiate the hepato-toxicity of halogenated hydrocarbons and inhibit aromatic hydrocarbon metabolism. 

Many halogenated hydrocarbons exert toxicity in their native form whereas others are more toxic and exert effects from the intermediates and metabolites formed in the biotransformation for excretion or other purposes. A special group of intermediates or by-products that are formed are different types of very reactive macromolecule and tissue-harming free radicals from carbon, oxygen and chlorine and organic radicals such as CHj", as well as hydrogen peroxide, epoxides and other electrophilic compounds emanating from the oxidative metabolism. 

Biotransformation of certain chlorinated hydrocarbon insecticides results in their conversion to metabolites which are less polar than the parent chemical. Heptachlor and aldrin are converted to the more lipophilic compounds heptachlor epoxide and dieldrin, respectively, whereas DDT is converted to DDE. The primary residue of DDT, which persists to the present day in animals and humans after exposure over a decade ago, is DDE. Following biotransformation, these compounds distribute to tissues which are higher in neutral lipid content than are the major organs of metabolism and excretion, the liver and kidney. These lipid-rich tissues are relatively, deficient in the so-called mixed-function oxidase (MFO) enzyme systems necessary for biotransformation of the halogenated hydrocarbons to more polar and thus more easily excreted compounds. As a result, these lipophilic chemicals remain unchanged in adipose tissue with only limited amounts returning to the circulation for possible metabolism and excretion. Paradoxically, aldrin and heptachlor metabolism results in an increased rather than reduced body load. This is opposite of the pattern seen for most other pesticide classes. 

The different Cl and CI2 compounds, summarized as halogenated hydrocarbons, are metabolized and excreted via urine or milk, or they are lost through expiration. However, the fate of these compounds depends on their specific characteristics (solubility, affinity to fat, liberation of Cl ). Polychlorinated dioxins and biphenyls are stored in fatty tissues. Among European people, typical levels of 30 ng TEQ diox-inskg fatty tissues have been estimated (TEQ = toxicity equivalence factor in comparison to 2,3,7,8-tetrachlordibenzodioxin Eorth et al. 2001). These substances are mobilized, for example at the onset of the... 

Aliphatic halogenated hydrocarbons Anaesthetizing irritant to mucous membranes liver damage kidney damage impaired vision loss of consciousness sometimes convulsions, oedema, death some compounds are carcinogenic Effects depend on the nature of the halogen atoms excretion almost exclusively after metabolism Chemical industry solvents refrigeration plant... 

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