PRINCIPLES OF TOXICOLOGY

poisoning. However, many of these compounds do not readily release cyanide once absorbed and their
toxicity cannot simply be characterized as that of cyanide itself. Systemic toxic effects among the
unsaturated nitriles are similar but, as noted previously for other series of organic solvents, the
unsaturated 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 number
of occupational and environmental regulatory agencies, based primarily on the data from animal studies.
16.17 TOXIC PROPERTIES OF THE PYRIDINE SERIES
Pyridine (see Figure 16.35) is the parent compound for the pyridine series of substituted analogs. It is
a flammable, unsaturated six-membered ring resembling benzene, but consisting of five carbons and
one nitrogen, as opposed to six carbons (see Section 16.5). The compound exhibits an extremely
objectionable, nauseating odor. For most substituted benzene compounds there is an analogous
compound in the pyridine series. Pyridine and its derivatives are used as solvents and raw materials in
the 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 the
gastrointestinal tract, peritoneal cavity, lungs, and from intact skin. The metabolic fate is not completely
known, but hydroxylation, N-methylation, oxidation, and conjugation reactions have been identified.
Reported elimination is rapid, limiting the potential for accumulation in tissues. Despite its wide
industrial 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 a
photosensitizer. 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, kidney
damage, 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 SOLVENTS
16.18 SULFUR-SUBSTITUTED SOLVENTS 405
Figure 16.34 Nitrile compounds.
Dimethyl sulfoxide (DMSO) (see Figure 16.36) is an industrial solvent that also has a wide applicability
in the pharmaceutical area to solubilize water-insoluble medication. It has the ability to carry solutes
into the skin’s stratum corneum from which they are slowly released into the blood and lymph system.
Figure 16.35 Pyridine.