PRINCIPLES OF TOXICOLOGY

398 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTS
16.14 TOXIC PROPERTIES OF REPRESENTATIVE NITROGEN-SUBSTITUTED
SOLVENTS
The 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 and
pigments, and are also used in the chemical, textile, rubber, and paper industries. Some aromatic nitro
compounds are used as dyestuffs while others, such as trinitrotoluene and pyridine, are used in
manufacture of chemical explosives. Pyrrolidine, morpholine, aniline, pyridine, and similar compounds
are used in crop protection as herbicides, fungicides, or insecticides. Still other nitrogen
substituted compounds are used as drugs and research tools. Finally, both β-chloroethylamine and
trichloronitromethane are strong irritants, and have been used for this purpose as effective chemical
warfare 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 amine
substituent. The corrosive properties generally are unrelated to the molecular size, in contrast to most
other organic chemical groups (e.g., esters, ethers, alcohols), which exhibit decreasing irritancy as
molecular size increases. The aliphatic amines are well absorbed by all routes of exposure. Thus, in
addition to physical damage to the skin, they may cause systemic toxicity, including methemoglobinemia,
pulmonary hemorrhage, hepatic necrosis, nephrotoxicity, and cardiac degeneration. In
addition, amines may mimic the physiologic effect of adrenaline (epinephrine), which has a similar
structure.
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 gastrointestinal
tract. The following list summarizes general toxicological properties of the alkyl amines:
• Irritancy increases up to six carbons, then decreases with further increasing molecular
weight.
• Unsaturated congeners are well absorbed following dermal exposure, while saturated
congeners are not.
• Direct irritant potential is not affected by other functional groups, although sensitization
potential 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 potential
handling hazard than most of the other chemical classes discussed in this chapter. Their strong irritant
properties stem from the fact that the amine portion of the molecule is a very corrosive functional
constituent. The skin has some resistance to changes in pH and can withstand chemical attack in the
pH range of 1–10 for short periods without significant damage. However, if the base strength of the
chemical is much above 10 or the acid has a pH lower than 1, significant skin injury may occur very
quickly after initial contact with the chemical. The base strength of most of the simple amines is in the
immediately 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 little
effect on the corrosiveness of the amine group. Thus, while the irritant nature of the other functional
groups (alcohols, ethers, carboxylic acids, etc.) is decreased as the size of the organic portion of the
chemical increases, the irritation of the amines is not affected.
Figure 16.26 Amine compounds.