PRINCIPLES OF TOXICOLOGY

400 PROPERTIES AND EFFECTS OF ORGANIC SOLVENTS
within the body, and it consists of a propylamine side chain attached to a catechol ring. Thus, it is easy
to understand why some of the alkyl amines may be able to mimic some epinephrine physiologic
responses. Following is a list of some of the general conclusions about alkyl amine-induced sympathomimetic
activity:
• Activity increases with the size of the alkyl chain, up to six carbons
• For alkylamines over six carbons, heart rate decrease and blood vessel dilation is more
common
• A branching of the alkyl carbon chain decreases activity of the chemical
• Pressor activity (blood vessel constriction) varies with structure
• Repeated exposure causes cardiac depression and vasodilation
• Convulsions may cause mortality at high, acute, repeated exposure
Human exposure to amine compounds should be avoided where possible, since a number of these
chemicals are regulated as demonstrated carcinogens. In particular, this includes the aromatic or
diphenylamine compounds such as the dye components benzidine, 2-naphthylamine, or 4-aminobiphenyl,
all of which induce bladder tumors. Other amine compounds may exhibit carcinogenic
potential as well, including the alkyl amine group of nitrosamines. The nitrosamines, potential liver
carcinogens, represent an interesting human risk issue, since any alkyl amine (including those
generated during the digestion of food) absorbed orally theoretically may be converted to a nitrosamine
by the acid and nitrite found in the gut. However, animal studies have failed to demonstrate that this
is a significant problem in humans.
In summary, the amines are very toxic substances presenting diverse dermal and handling hazards.
The following general characteristics apply:
• Irritation increases to six carbons, then decreases with loss in volatility
• For smaller alkylamines, irritantcy is not related to degree of substitution
• Unsaturated amines have greater systemic and dermal toxicity
• Irritation by these chemicals is not usually affected by functional groups
• Salts of amine chemicals are usually weaker irritants
• Additional functional groups may increase sensitization potential
• Sensitization is greater in aromatic amines
• Aromatic rings do not decrease the various toxicities
• Aromatic rings add methemoglobinemia and cancer as potential hazards
Aromatic Amino Compounds
The aromatic amino compounds are aromatic hydrocarbons in which at least one hydrogen atom has
been replaced by an amino group. The aromatic amines are synthesized by nitration of the aromatic
hydrocarbon with subsequent reduction to the amine or by the reaction of ammonia and a chloro- or
hydroxyhydrocarbon. Most of the aromatic nitro compounds are fat-soluble and water-insoluble such
that they readily penetrate the skin and can quickly be absorbed through the lungs and into the blood,
immediately becoming systemic in action. The most dominant toxic effects of the aromatic amino
compounds are methemoglobin formation and cancer of the urinary tract. Other toxic effects include
hematuria, cystitis, anemia, and skin sensitization. It is thought that the aromatic amines act indirectly
on methemoglobin formation through their metabolites. Most of the compounds are absorbed through
the skin and through respiration.