PRINCIPLES OF TOXICOLOGY

Despite its occasional consumption for that purpose, inebriation is not a prominent symptom of methanol
intoxication, unless an extreme quantity is consumed. It is significant that if ethanol is simultaneously
ingested in sufficient quantity, methanol poisoning may be considerably delayed, or even averted completely.
The subsequent administration of ethanol after methanol intake forms the basis for treatment of methanol
poisoning, based on competition for the same metabolic enzyme system (alcohol dehydrogenase).
Acute methanol poisoning is characterized by headache, vertigo, vomiting, upper abdominal pain,
back pain, dyspnea, restlessness, cold or clammy extremities, blurred vision, ocular hyperemia, and
diarrhea. Visual disturbance can proceed to blindness. The pulse may slow in severely ill patients, and
coma can develop rapidly. Death may be sudden, with accompanying inspiratory apnea and convulsions,
or may occur only after long coma, depending on circumstances of exposure.
The rate of methanol oxidation is only about 10–15 percent that of ethanol; therefore, complete
oxidation and excretion may require several days. An asymptomatic latent period of up to 36 hours
may precede the onset of adverse effects. As little as 15 mL of methanol reportedly has caused
blindness, and several ounces (70–100 mL) may be fatal. Aside from the well-described ocular effects,
neurologic damage of various types may follow methanol poisoning.
Ethyl alcohol (ethanol) (see Figure 16.6) in high concentrations acts as a mild to moderate
local irritant, having the ability to injure cells by precipitation and dehydration. The CNS typically
is affected more markedly than other systems. The initial apparent stimulation that accompanies
ethanol ingestion results from altered activity in areas of the brain that have been freed of
inhibition through the depression of control mechanisms. Ethanol increases the pain threshold
considerably in most individuals even at moderate doses.
Vasodilation of cutaneous blood vessels, resulting in flushing, may accompany ethanol ingestion.
Because of this, and despite folklore to the contrary, its use is contraindicated during hypothermia or
exposure to cold. Another principal acute effect is cardiovascular depression of CNS origin. It may
directly damage tissues at high chronic doses, producing skeletal myopathy and cardiomyopathy.
Because ethanol increases gastric secretion at high doses, it has been linked to erosive gastritis, which
can, in turn, increase the severity of ulcers. It promotes fat accumulation in the liver in some circumstances,
and chronic intake may lead to cirrhosis, liver cancer, or lethality. It promotes urine flow by
inhibiting the release of steroids and adrenaline from the adrenal glands. Ethanol may exert a direct
depressant action on bone marrow and may lead to a depression of leukocyte levels in inflamed areas,
which may explain in part the poor resistance to infection that often is reported in alcoholic individuals.
Other Simple Alcohols
16.6 TOXIC PROPERTIES OF REPRESENTATIVE ALCOHOLS 383
Aside from the common examples of methanol and ethanol, high concentrations of propanols (propyl
alcohols; structural variants including isopropanol, n-propanol) may cause intoxication and CNS
depression. They also have bactericidal properties.
Isopropanol [(CH 3 ) 2 CHOH] generally is less toxic than n-propanol [CH 3 (CH 2 ) 2 OH], but both
substances are more acutely toxic than ethanol. In humans, brief exposure to several hundred parts per
million of isopropyl alcohol in air generally causes mild irritation of eyes, nose, and throat. n-Butanol
(C 4 H 9 OH) is potentially more toxic than the lower-molecular-weight homologs, but it also is less
volatile, a fact that limits airborne exposure in most circumstances. Its symptoms may include eye,
Figure 16.6 Ethanol.