Page 341 - Industrial Ventilation Design Guidebook

S.3 TOXICiTY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 297

in myocytes (cardiac muscle cells) causing permanent functional and morpho-
logical alterations; and (3) the reaction is mediated through immunoiogical
mechanisms. Also, a reactive intermediate of ailylamine, acrolein, may cause
cardiac damage. When cardiac injury is mediated through immunoiogical
mechanisms, the reaction is usually due to the formation of a complex of the
chemical compound with some protein, also termed a hapten. 145
Mean arterial pressure and cardiac output, an expression of the amount of
blood that the heart pumps each minute, are the key indicators of the normal
functioning of the cardiovascular system. Mean arterial pressure is strictly con-
trolled, but by changing the cardiac output, a person can adapt, e.g., to in-
creased oxygen requirement due to increased workload. Blood flow in vital
organs may vary for many reasons, but is usually due to decreased cardiac out-
put. However, there can be very dramatic changes in blood pressure, e.g., blood
pressure plummets during an anaphylactic allergic reaction. Also cytotoxic
chemicals, such as heavy metals, may decrease the blood pressure.

Compounds Causing Cardiovascular Toxicity Alcohols are the most
important compounds causing vascular toxicity. Ethanol depresses cardiac
muscle and attenuates its contractivity when the concentration of ethanol in
the blood exceeds 0.75 mg/100 mL. Ethanol also causes arrhythmias, and a
metabolite of ethanol, acetaldehyde, also depresses the heart. Furthermore,
high concentrations of acetaldehyde cause cardiac arrhythmias. The cardio-
vascular toxicity of methanol is about the same as that of ethanol, whereas al-
cohols with longer chains are more toxic than ethanol.
Haiogenated hydrocarbons depress cardiac contractility, decrease heart
rate, and inhibit conductivity in the cardiac conducting system. The cardiac
toxicity of these compounds is related to the number of halogen atoms; it in-
creases first as the number of halogen atoms increases, but decreases after
achieving the maximum toxicity when four halogen atoms are present. Some
of these compounds, e.g., chloroform, carbon tetrachloride, and trichloroeth-
ylene, sensitize the heart to catecholamines (adrenaline and noradrenaline)
and thus increase the risk of cardiac arrhythmia.
Some metals, such as cadmium, cobalt, and lead, are selectively car-
diotoxic. They depress contractivity and slow down conduction in the cardiac
system. They may also cause morphological alterations, e.g., cobalt, which
was once used to prevent excessive foam formation in beers, caused cardiomy-
opathy among heavy beer drinkers. Some of the metals also block ion chan-
nels in myocytes. Manganese and nickel block calcium channels, whereas
barium is a strong inducer of cardiac arrhythmia.
Several chemical compounds may cause inflammation or constriction of
the blood vessel wall (vasoconstriction). Ergot alkaloids at high doses cause
constriction and thickening of the vessel wall. Ailylamine may also induce
constriction of coronary arteries, thickening of their smooth muscle walls, and
a disease state that corresponds to coronary heart disease. The culprit is a
toxic reactive metabolite of ailylamine, acrolein, that binds covalently to nu-
cleophilic groups of proteins and nucleic acids in the cardiac myocytes. i45
Atherosclerosis is a degenerative disease which is characterized by cholesterol-
containing thickening of arterial walls. Saturated fatty acids, high levels of choles-
terol, elevated blood pressure, and elevated serum lipoprotein are well-known risk