PRINCIPLES OF TOXICOLOGY - Biology East Borneo

16.18 SULFUR-SUBSTITUTED SOLVENTS 405Figure 16.34 Nitrile compounds.poisoning. However, many of these compounds do not readily release cyanide once absorbed and theirtoxicity cannot simply be characterized as that of cyanide itself. Systemic toxic effects among theunsaturated nitriles are similar but, as noted previously for other series of organic solvents, theunsaturated forms are more irritating than the corresponding saturated homolog.The most commonly used of the nitriles, acrylonitrile, is regulated as a suspected carcinogen by a numberof occupational and environmental regulatory agencies, based primarily on the data from animal studies.16.17 TOXIC PROPERTIES OF THE PYRIDINE SERIESPyridine (see Figure 16.35) is the parent compound for the pyridine series of substituted analogs. It isa flammable, unsaturated six-membered ring resembling benzene, but consisting of five carbons andone nitrogen, as opposed to six carbons (see Section 16.5). The compound exhibits an extremelyobjectionable, nauseating odor. For most substituted benzene compounds there is an analogouscompound in the pyridine series. Pyridine and its derivatives are used as solvents and raw materials inthe manufacture of chemicals, explosives, paints, disinfectants, herbicides, insecticides, antihistamines,and vitamins. Use of pyridine as a therapeutic agent in epilepsy treatment has been reported.The alkyl pyridine derivatives, as well as the parent molecule, are well absorbed from thegastrointestinal tract, peritoneal cavity, lungs, and from intact skin. The metabolic fate is not completelyknown, but hydroxylation, N-methylation, oxidation, and conjugation reactions have been identified.Reported elimination is rapid, limiting the potential for accumulation in tissues. Despite its wideindustrial application and limited medicinal use, reports of human poisoning are uncommon.Pyridine principally exerts its adverse effects on the central nervous system, gastrointestinal tract,liver, and kidneys. Local skin irritation also has been reported and pyridine has been reported to be aphotosensitizer. Inhalation exposure to pyridine at 125 ppm, 4 h per day for 2 weeks caused anorexia,nausea, vomiting, gastric distress, headache, fatigue, faintness, and depression. Hepatotoxicity, kidneydamage, and death were reported in cases where the dose was in excess of 2 mL/day for 2 months(approximately 0.029 mg/kg⋅day). Inhalation of vapor irritates the mucus membranes.16.18 SULFUR-SUBSTITUTED SOLVENTSDimethyl sulfoxide (DMSO) (see Figure 16.36) is an industrial solvent that also has a wide applicabilityin the pharmaceutical area to solubilize water-insoluble medication. It has the ability to carry solutesinto the skin’s stratum corneum from which they are slowly released into the blood and lymph system.Figure 16.35 Pyridine.