PRINCIPLES OF TOXICOLOGY

16.14 TOXIC PROPERTIES OF REPRESENTATIVE NITROGEN-SUBSTITUTED SOLVENTS 399
TABLE 16.6 Relative Base Strength of the Amines
Amine Compound Base Strength (pK)
Methylamine 10.6
Dimethylamine 10.6
Trimethylamine 10.7
Ethylamine 10.8
Diethylamine 11.0
Triethylamine 10.7
Propylamine 10.6
Butylamine 10.6
Allylamine 9.5
Cyclohexylamine 10.5
A characteristic of the amines that influences their acute toxicity and handling hazards is that they
are well absorbed by all routes. Thus, they represent a significant dermal hazard not only because of
the skin injuries they produce, but also because they tend to penetrate skin easily enough that the lethal
or acutely toxic dose whether the dose is taken in via the oral or the dermal route. Therefore, contact
with the skin should be avoided. Accompanying Table 16.7 summarizes the dose response. Note that
LD 50 is the amount lethal to 50 percent of the animals tested. Necrosis means cell or tissue death.
Because of their tissue-penetrative and tissue-corrosive characteristics, amines are toxic to all
tissues in which they are absorbed in measurable amounts and adversely affect a number of organs.
What organs will be most affected probably depends to a large extent on the distribution of the chemical
within the body. Some of the systemic effects observed for lethal exposures are edema and hemorrhage
of the lungs, necrosis of the liver, necrosis and nephritis in the kidneys, and muscular degeneration of
the heart.
Two other common characteristics observed in amine compounds are methemoglobin formation
in the red blood cells (see Chapter 4), and sensitization to the chemical itself. Sensitization to amines
probably happens because the amine group is fairly reactive. The chemicals may bind to cellular
proteins to form haptens, or molecules that go unrecognized by the body’s immune defenses. The body
produces antibodies against these haptens, and on subsequent chemical exposure an allergic reaction
may ensue. During this antibody-hapten response, the body releases histamine, which, in turn, induces
arterial vasoconstriction, capillary dilation, a fall in blood pressure, itching, and a bronchoconstriction.
These effects explain many of the effects seen in a severe allergic response: labored or difficult
breathing, fainting or possibly anaphylactic shock, and a reddening or irritation-like response where
contact with the skin has occurred. Some of the amine compounds are potent sensitizers, and dermal
exposure should be avoided.
A somewhat uncommon feature of the alkyl amines is their ability to simulate the actions of
epinephrine (or adrenaline) within the body. Epinephrine is an important neurohormonal transmitter
TABLE 16.7 Relative Toxicity of the Amines a
Amine Oral LD50 (mg/kg) Skin LD50 (mg/kg) Dermal Effects
Methylamine 0.02 0.04 Necrosis
Ethylamine 0.4 0.4 Necrosis
Propylamine 0.4 0.4 Necrosis
Butylamine 0.5 0.5 Necrosis
Hexylamine 0.7 0.4 Slight necrosis
a Note that LD50 is the amount lethal to 50 percent of the animals tested. Necrosis means cell or tissue death.