5.0 CARCINOGENS, MUTAGENS, EMBRYOTOXINS
Cancer is the second leading cause of death in the United States. Approximately 25% of the population will develop some form of cancer during their lifetime. Cancer is not a single disease, but a group of diseases characterized by uncontrolled growth of abnormal cells. These cells are destructive and often can migrate to new sites to form secondary growths. Among the causes of cancer, environmental agents acting in combination with genetic susceptibilities are believed to be the most prominent. Approximately 60% to 90% of all cancers may be related to environmental factors such as sunlight, radiation, chemicals, diet, and viruses.
Agents that cause cancer or increase the risk of cancer either by initiating or promoting it, are called carcinogens. Carcinogens can enter the body through the skin, lungs, or the digestive system and interact with the body by direct or indirect means. Direct acting carcinogens usually cause cancer at the site of exposure, for example, skin contact with coke oven emissions may cause skin cancer. Indirect acting carcinogens are changed by the body into carcinogenic substances that cause cancer at sites other than the initial exposure site. Common examples include solvents such as benzene and carbon tetrachloride. Other substances, called promoters, do not cause cancer themselves but are necessary for some chemicals to express their carcinogenicity.
Chemical carcinogens were among the first agents associated with an increased incidence of cancer. In 1775, a positive association was demonstrated between exposure to soot and scrotum cancer among chimney sweeps in England. Since then, chemical components of tar, smoke, air pollution, and automobile exhausts have been shown to be carcinogenic. Several occupational chemicals are carcinogens, including asbestos, arsenic, benzene, beryllium, and cadmium.
Carcinogens differ in the length of time needed for the cancer to develop after the initial exposure. This latency period may be as short as five years for the development of leukemia from benzene exposure to as long as 20 years to develop lung cancer from cigarette smoking.
The existence of a safe level or threshold has not been demonstrated for most carcinogens. Because of this, it must be assumed that low doses can cause cancer also but at a proportionately lower rate than high doses. Therefore, it is prudent to reduce exposures to known or suspected carcinogens to the lowest level possible. Exposure to several carcinogens at once may result in cancer rates higher than would be expected by adding the risks from each carcinogen separately. This is known as a synergistic effect. For example, both cigarette smoking and exposure to asbestos have been show to cause cancer. The cancer rate among asbestos workers who smoke is much greater than would be expected by adding the risk from smoking to the risk from asbestos.
The mechanism that causes a normal cell to become cancerous is not well understood. The process is usually characterized by three stages: initiation, promotion, and progression. During the initiation stage, the DNA in the cell that carries the genetic information for cell division is altered either spontaneously or by an external agent. This altered cell may replicate during the promotion stage into a malignant tumor. The appearance of the tumor following initiation may take 5-30 years. This latency period is probably related to a gradual weakening of the immune system or hormonal changes as the body ages. Another theory states that the cells remain dormant until another stimulus from an environmental agent causes it to start dividing. During the progression stage, the tumor invades adjoining tissue and may spread throughout the body.
OSHA considers a chemical to be a carcinogen if the chemical causes cancer in humans or two different mammal species. The carcinogenic potential of a chemical in humans is usually discovered through epidemiological (population) studies. In these studies, the incidence of cancer in a group of exposed workers is compared to a comparable unexposed population. For example, when compared to unexposed workers, an excess of liver cancer was found among PVC workers and an excess of lung cancer was found in asbestos workers. Another study on members of the American Chemical Society has shown a significantly higher incidence of cancer deaths among chemists than would be expected in the general population.
Human population studies are not always adequate to determine if a chemical is carcinogenic. Large populations are needed, cancers may not develop for 30 years, and there are many variables that must be controlled. Therefore, tests are usually performed on experimental animals under controlled conditions. Tests on animals can identify human carcinogens because chemicals that cause cancers in one mammalian species are likely to cause cancers in another. Except arsenic, all human carcinogens have also been demonstrated to be carcinogenic in animals. It must be assumed that agents that cause cancers in animals are likely to be carcinogenic in humans.
Animal studies are performed to demonstrate the potential for a chemical to cause cancer. Because small populations are used, it is necessary to use large doses of chemicals to demonstrate an effect. This does not mean that only large doses of the chemical will cause cancer. Smaller doses would cause cancer also but in proportionately smaller numbers, numbers so small that they might be missed in a small population.
Screening tests using cells growing in laboratory cultures, require only a few days or weeks to provide preliminary results on the carcinogenic potential of chemicals. The suspect chemical is added to the cells and any mutation is noted. Approximately 90% of chemicals found to be carcinogenic in humans or animals have also shown mutagenic changes in these tests.
Chemical carcinogens are commonly found in the following groups. Carcinogenic chemicals should also be considered mutagenic.
Polycyclic aromatic hydrocarbons (PAHs). PAHs were the first group of chemicals shown to be carcinogenic in man. PAHs are produced from the combustion of fossil fuels and tobacco. PAHs are probably the most widespread chemical carcinogens in the environment and some of the most powerful carcinogens are found in this group.
Nitroso compounds. Nitroso compounds are widely distributed in the environment and can also form in the body. These compounds may be one of the most important groups of carcinogens in man. Sodium nitrite is a commonly used preservative in meat that is converted to carcinogenic nitrosamines in the body.
Halogenated hydrocarbons. Several of these compounds are commonly used as solvents. Examples include carbon tetrachloride, chloroform, trichloroethylene, and methylene chloride.
Inorganic metals and minerals. Several carcinogens are known among metals or their salts. Examples of these include beryllium, cadmium, nickel, cobalt, and chromium. Only two minerals are known to cause cancer: asbestos and arsenic.
Naturally occurring. Several natural occurring carcinogens are known. Among these is aflatoxin, probably the most potent of all carcinogens. Aflatoxins are produced by molds that grow on peanuts and corn. Other naturally occurring carcinogens are present in sassafrass and chili peppers.
Mutagenic substances cause an alteration in the genetic instructions on the DNA molecule. If the alteration occurred on a somatic (non-sex cell) the results could be the development of cancer. An alteration of a germ cell (sex cell) in either sex can produce genetic defects that will be transmitted to the next generation. Since all genes are composed of DNA, a mutagenic substance that can produce alterations in one species is considered capable of producing alterations in another.
Because approximately 90% of chemical carcinogens have been shown to be mutagenic, the carcinogenic potential of a chemical can be determined by assessing its ability to produce mutations. The potential mutagenic potential of a chemical can be rapidly determined by performing short term "in vitro" (in the tube) tests. In vitro tests use a microbial organism, such as a bacterium, to assess the potential of a chemical to produce alterations in the genetic material and produce mutations. This procedure is commonly known as the Ames Test.
Long term "in vivo" (in the animal) studies are only needed for a few chemicals. Insects, mice, rats, and hamsters are used for these tests to evaluate mutagenicity in an animal system. Chemicals producing positive animal results can be considered a genetic risk for humans.
Women of child bearing potential must be especially concerned about exposure to hazardous chemicals because many chemicals may be hazardous to the embryo or fetus. Embryotoxins are substances that may kill, deform, retard the growth, affect the development of specific functions in the unborn child, or cause postnatal functional problems. Agents that only produce malformations of the embryo are called teratogenic. Approximately 60-70% of all malformations are the result of chemical, physical and infectious agents. The developing embryo depends on the environment to supply the substances needed for growth and differentiation of the tissues and organs of the embryo. Because of this, various chemical, physical, and infectious agents may alter or arrest growth in the developing embryo.
The influence of embryotoxins depends on when the exposure took place. The period of greatest susceptibility to embryotoxins is the first trimester, which includes a period when the woman may not know she is pregnant. The embryo is undergoing rapid growth and differentiation and significant malformations can be produced. Although the development of the fetus is not as sensitive as the embryo, alterations may still occur, particularly in the nervous system.
Medicines. Medicines that have been shown to be embryotoxic in humans include thalidomide, diethylstilbestriol, some male hormones similar to methyltestosterone, and some anticancer drugs.
Solvents. Growth retardation and abortions, but not malformations, have been shown in animals exposed to chloroform, carbon tetrachloride, trichloroethylene, perchloroethylene, benzene, xylene, and propylene glycol.
Heavy metals. Organomercurials and lead compounds have demonstrated embryotoxic properties in humans. Cadmium, arsenic, selenium, chromium, and nickel compounds have been shown to be embryotoxic in animals and are classified as potentially harmful to the human embryo.
Pesticides. Pesticides producing malformations in animals include parathion, demeton, paraquat, and penthion.
Anesthetic gases. Anesthetic gases demonstrating embryotoxic properties in animals include ethylene oxide, and nitrous oxide.
Organic compounds. Organic compounds that have shown embryotoxic properties in animals include azo dyes, and formaldehyde.
SAFETY PROCEDURES FOR HANDLING CARCINOGENS
The following procedures should also be used when working with highly toxic chemicals, mutagens, and embryotoxins.
Protective clothing. Protective clothing such as a fully fastened laboratory coat and disposable gloves should be worn to prevent contact of carcinogenic chemicals with the skin. Contaminated clothing should not be worn out of the work area.
Protective equipment. Appropriate eye protection should be available and used in the work area. Contact lenses should not be worn. Appropriate respiratory equipment should be worn if the procedure generates airborne particulates or gases. The face mask or respirator should not be worn out of the work area.
Eating, drinking, & smoking. There shall be no eating, drinking, smoking, chewing of gum or tobacco, or application of cosmetics in areas where carcinogenic chemicals are used or stored. Storage of food or food containers in these areas is also prohibited.
Pipetting. Under no circumstances is oral pipetting of carcinogenic chemicals permitted. Pipetting should always be performed with the aid of a mechanical pipetting device.
Personal hygiene. Workers should wash their hands immediately after the completion of any procedure involving the use of carcinogenic materials.
Storage. Carcinogens should be stored in a designated area or cabinet and posted with the appropriate hazard sign. Volatile chemicals should be stored in a ventilated storage area in a secondary container having sufficient volume to contain the material in case of an accident. Storage areas should be separated from flammable solvents and corrosive liquids.
Labeling. All containers should be labeled as to contents and bear the appropriate hazard warning information.
Containment. Procedures involving the use of volatile chemical carcinogens or procedures that may generate aerosols should be conducted in a chemical fume hood or glove box. Procedures involving non-volatile compounds and procedures with a low aerosol potential should be done in a controlled area that is designated for carcinogenic materials.
Transport. Carcinogens should be transported in unbreakable outer covers such as metal cans. Contaminated materials that are to be transported to a disposal area should be placed in a plastic bag or other impervious material, sealed, and labeled appropriately before transport.
Housekeeping. To minimize the production of aerosols, dry mopping and dry sweeping should not be done in areas where finely divided solid carcinogens are used. Wet mopping or a vacuum cleaner equipped with a HEPA filter should be used.
Working quantities. Working quantities (outside of storage) should be kept to a minimum and should not exceed the amounts required for use in one week.
Spill control. Spills and accidents must be immediately reported to supervisory personnel and to the Safety Office. Because of aerosol production, the area should be evacuated immediately unless the spill is small and well contained. Personnel performing decontamination should wear adequate protective clothing including respirators or self-contained breathing apparatus. As much of the spill as possible should be absorbed into paper towels, rags or sponges. Dry solids should be covered with paper towels moistened with water or an appropriate solvent. Care should be taken not to generate aerosols. Large spills may require a HEPA filtered vacuum cleaner. Decontamination of the spill should be attempted only after the bulk of the spill has been removed by mechanical means.
Disposal. Volatile carcinogens should never be disposed of by evaporation. Chemicals and contaminated materials should be decontaminated or removed for subsequent disposal. Contaminated waste, and cleaning devices should be collected in plastic bags or other impervious containers, sealed, labeled as to contents and hazard and disposed of by approved methods.
Handwashing facilities. Handwashing facilities should be available in the work area where carcinogens are used. Foot or elbow operated faucets are preferable.
Eye-wash & deluge showers. OSHA approved eye-wash units and deluge showers should be readily available to personnel working with carcinogens having corrosive properties or that can penetrate the skin.
Work area identification. Entrances to work areas where significant quantities of carcinogens are used or stored should be posted with a sign stating "Danger Carcinogen - Authorized Personnel Only." In addition, the area should also be posted with a sign stating "No Eating, Drinking, or Smoking."
Access. Only authorized personnel should be allowed in areas where carcinogens are used and stored. Casual visitors should be prohibited. Doors should be closed at all times.
Work surfaces. Work surfaces on which carcinogenic chemicals are handled should be protected from contamination by using an impervious material such as stainless steel, plastic trays or absorbent plastic backed paper. Work surfaces should be decontaminated or disposed of properly after the procedure has been completed.
6.0 FLAMMABLE LIQUIDS
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