Page 343 - Industrial Ventilation Design Guidebook

5.3 TOXICITY AND RISKS INDUCED BY OCCUPATIONAL EXPOSURE TO CHEMICAL COMPOUNDS 299

liver necrosis. Carbon tetrachloride, tetrachloroethylene, and yellow phosphorus in-
duce lipid peroxidation, one common mechanism of liver necrosis. There are, how-
ever, a number of compounds (e.g., dimethyl nitrosoamine) that cause liver necrosis
without causing lipid peroxidation. Recent findings suggest that neutrophil-mediated
cytotoxicity may play a role in some forms of liver toxicity, perhaps due to inflamma-
I47 148
tory mediators or reactive oxygen species excreted by these inflammatory cells. <
Accumulation of lipids in the liver (steatosis) is one possible mechanism
for liver toxicity. Several compounds causing necrosis of hepatocytes also
cause steatosis. There are, however, some doubts that steatosis would be the
primary cause of liver injury. Several compounds cause steatosis (e.g., puro-
mycin, cycloheximide) without causing liver injury. Most of the accumulated
lipids are triglycerides. In steatosis, the balance between the synthesis and ex-
cretion of these lipids has been disturbed (see Table 5.13). 147 148
-

TABLE 5. 1 3 Examples of Drugs that Induce Intrahepatic Cholestasis
or Liver Damage Resembling That Induced by Viral Hepatitis

Intrahepatic cholestasis Viral hepatitis-like liver damage
Amitriptyline Ethacrynic acid
Azathioprine Halothane
Carbamazepine Indomethacin
Chlorodiazepoxide Imipramine
Chlorpromazine Iproniazid
Chlorthiazide Carbamazepine
Diazepam Alphamethyldopa
Erythromycin estholate Nialamide
Estradiole Phenylbutazone
Ethacrynic acid Pyrazmamide
Fluphenazine Sulphamethoxazole
Haloperidol Isoniazid
Imipramine
Mestranole
1 7-methylnortestosterone
Methyl testosterone
Nitrofurantoin
Noretandrolone
Oxacillm
Oxandrolone
Penicillamine
Perphenazine
Perchloroperazine
Promazine
Thioridazine
Tolbutamide
Source: Modified from Savolainen and Vahakangas. 151