PRINCIPLES OF TOXICOLOGY - Biology East Borneo

398 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTS16.14 TOXIC PROPERTIES OF REPRESENTATIVE NITROGEN-SUBSTITUTEDSOLVENTSThe nitrogen substituted compounds have been used in a wide range of industrial applications.Aromatic amino compounds are important as intermediates in the manufacture of dyestuffs andpigments, and are also used in the chemical, textile, rubber, and paper industries. Some aromatic nitrocompounds are used as dyestuffs while others, such as trinitrotoluene and pyridine, are used inmanufacture of chemical explosives. Pyrrolidine, morpholine, aniline, pyridine, and similar compoundsare used in crop protection as herbicides, fungicides, or insecticides. Still other nitrogensubstituted compounds are used as drugs and research tools. Finally, both β-chloroethylamine andtrichloronitromethane are strong irritants, and have been used for this purpose as effective chemicalwarfare agents.The aliphatic amines (see Figure 16.26) are among the most toxic classes of organic chemicals.Most members are potent irritants and sensitizers, a property related to the base strength of the aminesubstituent. The corrosive properties generally are unrelated to the molecular size, in contrast to mostother organic chemical groups (e.g., esters, ethers, alcohols), which exhibit decreasing irritancy asmolecular size increases. The aliphatic amines are well absorbed by all routes of exposure. Thus, inaddition to physical damage to the skin, they may cause systemic toxicity, including methemoglobinemia,pulmonary hemorrhage, hepatic necrosis, nephrotoxicity, and cardiac degeneration. Inaddition, amines may mimic the physiologic effect of adrenaline (epinephrine), which has a similarstructure.The tumorigenic properties of the aliphatic amines generally are limited to the nitrosamines.However, it is thought that alkyl amines may be converted to the nitrosamine form in the gastrointestinaltract. The following list summarizes general toxicological properties of the alkyl amines:• Irritancy increases up to six carbons, then decreases with further increasing molecularweight.• Unsaturated congeners are well absorbed following dermal exposure, while saturatedcongeners are not.• Direct irritant potential is not affected by other functional groups, although sensitizationpotential may be altered.• Salts of aliphatic amines are typically weaker irritants than the parent molecule.As noted previously, they are strong irritants and therefore probably represent a greater potentialhandling hazard than most of the other chemical classes discussed in this chapter. Their strong irritantproperties stem from the fact that the amine portion of the molecule is a very corrosive functionalconstituent. The skin has some resistance to changes in pH and can withstand chemical attack in thepH range of 1–10 for short periods without significant damage. However, if the base strength of thechemical is much above 10 or the acid has a pH lower than 1, significant skin injury may occur veryquickly after initial contact with the chemical. The base strength of most of the simple amines is in theimmediately injurious range of pH greater than 10, as shown in Table 16.6.The molecular size and the degree of substitution (i.e., primary, secondary, or tertiary) have littleeffect on the corrosiveness of the amine group. Thus, while the irritant nature of the other functionalgroups (alcohols, ethers, carboxylic acids, etc.) is decreased as the size of the organic portion of thechemical increases, the irritation of the amines is not affected.Figure 16.26 Amine compounds.