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FIGURE 4.2 A simple representation of possible dose-response curves.

vapor pressure that inhalation is an important route of chemical entry into the body), the LC50 is often reported instead of the LD50. The LC50 is the concentration of the chemical in air that will kill 50% of the test animals exposed to it. The LC50 is given in parts per million, milligrams per liter, or milligrams per cubic meter. Also reported are LCLO and LDLO values, which are defined as the lowest concentration or dose that causes the death of test animals. In general, the larger the LD50 or LC50, the more chemical it takes to kill the test animals and, therefore, the lower the toxicity of the chemical. Although lethal dose values may vary among animal species and between animals and humans, chemicals that are highly toxic to animals are generally highly toxic to humans.

4.C.1.2 Duration and Frequency of Exposure

Toxic effects of chemicals occur after single (acute), intermittent (repeated), or long-term repeated (chronic) exposure. An acutely toxic substance causes damage as the result of a single short-duration exposure. Hydrogen cyanide, hydrogen sulfide, and nitrogen dioxide are examples of acute toxins. In contrast, a chronically toxic substance causes damage after repeated or long-duration exposure or causes damage that becomes evident only after a long latency period. Chronic toxins include all carcinogens, reproductive toxins, and certain heavy metals and their compounds. Many chronic toxins are extremely dangerous because of their long latency periods: the cumulative effect of low exposures to such substances may not become apparent for many years. Many chemicals may be hazardous both acutely and chronically depending on exposure level and duration.

In a general sense, the longer the duration of exposure, that is, the longer the body (or tissues in the body) is in contact with a chemical, the greater the opportunity for toxic effects to occur. Frequency of exposure also has an important influence on the nature and extent of toxicity. The total amount of a chemical required to produce a toxic effect is generally less for a single exposure than for intermittent or repeated exposures because many chemicals are eliminated from the body over time, because injuries are often repaired, and because tissues may adapt in response to repeated low-dose exposures. Some toxic effects occur only after long-term exposure because sufficient amounts of chemical cannot be attained in the tissue by a single exposure. Sometimes a chemical has to be present in a tissue for a considerable time to produce injury. For example, the neurotoxic and carcinogenic effects from exposure to heavy metals usually require long-term, repeated exposure.

The time between exposure to a chemical and onset of toxic effects varies depending on the chemical and the exposure. For example, the toxic effects of carbon monoxide, sodium cyanide, and carbon disulfide are evident within minutes. The chemical reaches the target organ rapidly and the organ responds rapidly. For many chemicals, the toxic effect is most severe between one and a few days after exposure. However, some chemicals produce delayed toxicity; in fact, the neurotoxicity produced by some chemicals is not observed until a few weeks after exposure. Delayed toxic effects are produced by chemical carcinogens and some organ toxins that produce progressive diseases such as pulmonary fibrosis and emphysema: in humans, it usually takes 10 to 30 years between exposure to a known human carcinogen and the detection of a tumor, and pulmonary fibrosis may take 10 or more years to result in symptoms.



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