PRINCIPLES OF TOXICOLOGY - Biology East Borneo

16.6 TOXIC PROPERTIES OF REPRESENTATIVE ALCOHOLS 383Despite its occasional consumption for that purpose, inebriation is not a prominent symptom of methanolintoxication, unless an extreme quantity is consumed. It is significant that if ethanol is simultaneouslyingested 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 methanolpoisoning, 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, anddiarrhea. Visual disturbance can proceed to blindness. The pulse may slow in severely ill patients, andcoma 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, completeoxidation and excretion may require several days. An asymptomatic latent period of up to 36 hoursmay precede the onset of adverse effects. As little as 15 mL of methanol reportedly has causedblindness, 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 moderatelocal irritant, having the ability to injure cells by precipitation and dehydration. The CNS typicallyis affected more markedly than other systems. The initial apparent stimulation that accompaniesethanol ingestion results from altered activity in areas of the brain that have been freed ofinhibition through the depression of control mechanisms. Ethanol increases the pain thresholdconsiderably 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 orexposure to cold. Another principal acute effect is cardiovascular depression of CNS origin. It maydirectly 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, whichcan, 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 byinhibiting the release of steroids and adrenaline from the adrenal glands. Ethanol may exert a directdepressant 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 AlcoholsAside from the common examples of methanol and ethanol, high concentrations of propanols (propylalcohols; structural variants including isopropanol, n-propanol) may cause intoxication and CNSdepression. They also have bactericidal properties.Isopropanol [(CH 3) 2CHOH] generally is less toxic than n-propanol [CH 3(CH 2) 2OH], but bothsubstances are more acutely toxic than ethanol. In humans, brief exposure to several hundred parts permillion of isopropyl alcohol in air generally causes mild irritation of eyes, nose, and throat. n-Butanol(C 4H 9OH) is potentially more toxic than the lower-molecular-weight homologs, but it also is lessvolatile, a fact that limits airborne exposure in most circumstances. Its symptoms may include eye,Figure 16.6 Ethanol.