PRINCIPLES OF TOXICOLOGY

16.10 TOXIC PROPERTIES OF REPRESENTATIVE CARBOXYLIC ACIDS 389
Figure 16.13 Ketone compounds.
Other Ketones
Methyl ethyl ketone (2-butanone; MEK) is a very common industrial raw material and
solvent. Uses include production of 1,3-butanedione and MEK peroxide. It is detectable by
odor at a few parts per million in air, which represents a reasonable warning property several
hundred times less than its occupational exposure guideline. High concentrations are irritating
to the eyes, nose, and throat, and dermal or ocular irritation will accompany exposure to
liquid splashed on the skin or in the eyes. CNS depression may result from prolonged
exposure. The toxicological literature concerning MEK is extensive both in the form of
animal studies and human exposure data.
Acetophenone (phenylethylketone) saw historical use as an anesthetic, but it is used today as a
component of perfumes because it has a persistent odor that is not unlike orange blossoms or jasmine.
It is a strong skin irritant, but it is not a potent CNS depressant. Eye contact may cause irritation and
transient corneal burns.
Methyl-n-butyl ketone is a potent neurotoxin under some exposure circumstances and is metabolized
to 2,5-hexanedione, which also is the neurotoxic metabolite that has been attributed to hexane.
Therefore, it may induce a polyneuropathy like that described previously for hexane.
Industrially important exposures to ketones may be evaluated by urinary measurement of the
relevant chemical (e.g., acetone, MEK, methyl isobutyl ketone).
16.10 TOXIC PROPERTIES OF REPRESENTATIVE CARBOXYLIC ACIDS
As with aldehydes and ketones, the irritant properties of these compounds dominate the observed
effects and may mask CNS-depressant potential. The acidity (low pH), and therefore irritancy,
decreases with increasing molecular size. Halogenation of carboxylic acids (see Figure 16.15)
increases the strength of the acid and makes a stronger irritant. Dicarboxylic acids and unsaturated
carboxylic acids are comparatively more corrosive. Hydroxyl or halogen substitution at the
α-carbon enhances irritant potential. For example, acetic acid (CH 3 COOH) is moderately irritating,
but the unsaturated acrylic acid (CH 2 ?CHCOOH) and crotonic acid (CH 3 CH?CHCOOH),
or trichloroacetic acid (CCl 3 COOH; a mammalian metabolite of trichloroethene), may produce
burns and tissue damage.
Figure 16.14 Acetone.