Page 342 - Industrial Ventilation Design Guidebook

298 CHAPTER 5 PHYSIOLOGICAL AND TOXICOLOGICAL CONSIDERATIONS

factors for atherosclerosis. Exposure to some chemical compounds, such as carbon
disulfide (CS 2) and CO may promote the development of the disease, 36

LiVer Toxiclty
The liver is the most important metabolizing organ in the body. It is largely re-
sponsible for the biotransformation of chemicals and drugs to water-soluble forms
that can be excreted in the urine or bile. The functional unit of the liver is the trian-
gular-shaped acinus, the tip of which is located between the terminal vein and adja-
61
cent portal arteries (see Fig. 5.49). Liver damage may cause dramatic changes in
the biotransformation of chemicals, and lead to alterations in metabolic pathways.
Severe liver damage is characterized by fibrosis and scar formation and the loss of
functional capacity of the organ. There are many chemical compounds capable of
l47 148
inducing liver damage. '
Yellow phosphorus was the first identified liver toxin. It causes accumula-
tion of lipids in the liver. Several liver toxins such as chloroform, carbon tetra-
chloride, and bromobenzene have since been identified. The forms of acute
liver toxicity are accumulation of lipids in the liver, hepatocellular necrosis, in-
trahepatic cholestasis, and a disease state that resembles viral hepatitis. The
types of chronic hepatotoxicity are cirrhosis and liver cancer.

Acute Liver Damage Several compounds (e.g., dimethyl nitrosoamme, car-
bon tetrachloride, and thioacetamide) cause necrosis of hepatocytes by inhibiting pro-
tein synthesis at the translational level, i.e., by inhibiting the addition of new amino
acids into the protein chain being synthetized. This is not, however, the only mecha-
nism. Ethionine is a compound which inhibits protein synthesis but does not induce

FIGURE 5.49 Schematic of liver operational units: the classic lobule and the acinus. 146 (See also
Fig. 5.38.)(Used with permission.)