Petroleum Products.

Gasoline, kerosene, mineral oil, and turpentine are highly volatile and are a common cause of poisoning in children. Inhalation of these vapors causes dizziness, incoordination, and central

nervous system depression.

Aromatic Hydrocarbons.

Benzene, toluene, and xylene are widely used solvents in the rubber and shoe industries and in printing and paper-coating. Although toluene and xylene are not carcinogenic, inhalation of

benzene is hazardous because it can cause bone marrow toxicity, aplastic anemia, and acute leukemia. Benzene is metabolized by the cytochrome P-450 system in liver, producing

benzoquinone and muconaldehyde. These metabolic products are believed to cause bone marrow toxicity.

Polycyclic Aromatic Hydrocarbons

Polycyclic aromatic hydrocarbons are among the most potent chemical carcinogens ( Chapter 7 ). The carcinogenicity of these compounds was recognized in 1775, with the description of

scrotal cancer in English chimney sweeps exposed to soot. A variety of polycyclic aromatic hydrocarbons characterized

by three or more fused benzene rings are produced by combustion of fossil fuels; high-temperature processing of coke, coal, and crude oil; and iron and steel foundries. Benzo[a]pyrene is

the prototype of polycyclic aromatic hydrocarbons. As described earlier (see Fig. 9-4A ), it is metabolized by cytochrome P-450, prostaglandin H synthetase, and epoxide hydrolase, an

inducible microsomal enzyme in the liver. Activated epoxide intermediates bind to DNA; these adducts have been used as markers of polycyclic aromatic hydrocarbon exposure.

Occupational exposure to polycyclic aromatic hydrocarbons is associated with an increased risk of lung and bladder cancers.[42] Cigarette smoking is another important source of benzo[a]

pyrene. Mutations in the p53 tumor-suppressor gene found in lung cancers associated with cigarette smoking are most commonly G:CÕT:A transversions. This mutational spectrum is

consistent with metabolism of benzo[a]pyrene to reactive intermediates that attack deoxyguanines on the nontranscribed DNA strand.[7]

Plastics, Rubber, and Polymers

Millions of tons of synthetic plastics, rubber, and polymers are produced throughout the world. These products are then fabricated into latex fabrics, pipe, cables, flooring, home and

recreational products, medical products, and containers. In 1974, occupational exposure to vinyl chloride monomers used to produce polyvinyl chloride resins was found to be associated

with angiosarcoma of the liver. Vinyl chloride is a colorless gas that is flammable and explosive. Before the polymerization step in the manufacturing of polyvinyl chloride, it can be

absorbed through the skin or lungs. Vinyl chloride is metabolized by the cytochrome P-450 system in the liver to chloroacetaldehyde. This metabolite covalently binds to DNA and is

mutagenic. Exposure of rubber workers to 1,3-butadiene

TABLE 9-13-- Toxic and Carcinogenic Metals

Date: 2016-04-22; view: 721