industrial exposure

For centuries, physicians have recognized that occupational exposures contribute to human disease. The spectrum of human diseases associated with occupational exposures is summarized in Table 9-12. Almost all organ systems can be affected, resulting in acute toxicity or irritation, hypersensitivity reactions, chronic toxicity, fibrosis, and cancer. The chronic effects of occupational exposures are complex; they include degenerative changes in the nervous system, reproductive dysfunction, lung fibrosis, and cancer. The mechanisms responsible for these effects are not well understood. Some examples of acute and chronic diseases resulting from occupational exposures and potential hazards of environmental exposures are discussed in the following sections.

Volatile Organic Compounds

Large volumes of organic solvents and vapors are used in industry and in homes. These chemicals are known as volatile organic compounds (VOCs). They are used in manufacturing, degreasing, and dry cleaning and as components of paint removers and aerosol sprays. VOCs and petroleum products such as kerosene, mineral oil, and turpentine are stored in underground tanks. Surface spills and leakage from storage tanks can cause contamination of underground water supplies. In general, high levels of exposure encountered in industry cause headache, dizziness, and liver or kidney toxicity. At lower levels of exposure, there is concern about potential carcinogenicity and adverse reproductive effects. Some VOCs and their adverse effects are described next.

 Aliphatic Hydrocarbons

These compounds are the most widely used industrial solvents and dry-cleaning agents. All of these chemicals are readily absorbed through the lungs, skin, and gastrointestinal tract. In addition to acute central nervous system depression, they can cause liver and kidney toxicity. Common examples of these chemicals are chloroform and carbon tetrachloride; both are carcinogenic in rodents. Methylene chloride, another such chemical, is used in paint removers and aerosols. In enclosed areas, high concentrations of methylene chloride can be reached because it is highly volatile. Methylene chloride is metabolized by cytochrome P-450 to carbon dioxide and carbon monoxide. Carbon monoxide can form carboxyhemoglobin, causing respiratory depression and death. Perchloroethylene and related compounds are widely used in the dry-cleaning industry. Acute exposure causes central nervous system depression, confusion, dizziness, impaired gait, and nausea. Repeated exposures may cause dermatitis. Perchloroethylene is a potential human carcinogen.

 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. 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.

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.

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:C→T:A transversions. This mutational spectrum is consistent with metabolism of benzo[a]pyrene to reactive intermediates that attack deoxyguanines on the nontranscribed DNA strand.

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 has been shown to be associated with an increased risk of leukemia. Plastics are widely used in consumer products, including food and beverage containers.

Public exposure to plasticizers, such as phthalate esters, and to additives such as bisphenol-A raises concern about potential adverse reproductive effects of these synthetic chemicals. Phthalate esters have been shown to induce testicular injury in rats, and bisphenol-A mimics the proliferative effects of estrogen.

Metals

Occupational exposure to metals in mining and manufacturing is associated with acute and chronic toxicity, as well as carcinogenicity.

Occupational as well as environmental exposure to lead continues to be a serious public health problem. Agricultural exposure to arsenic-containing pesticides is discussed subsequently.

 lead