Individuals differ in their response to chemicals and it is difficult to predict the dose that will cause a response in a particular individual. For this reason, it is practical to predict what percentage of a population will respond to a specific dose of a chemical.
For example, the dose at which 50% of the population dies is called the lethal dose 50, or LD-50. The LD-50 is a crude approximation of a chemical’s toxicity. It is a gruesome index that does not adequately convey the sophistication of modern toxicology and is of little use in setting a standard for toxicity. However, the LD-50 determination is required for new synthetic chemicals as a way of estimating their toxic potential. Table 1 shows the examples of LD-50 values in rodents for selected chemicals.
The ED-50 (effective dose 50%) is the dose that causes an effect in 50% of the population of observed subjects. For example, the ED-50 of aspirin would be the dose that relieves headaches in 50% of the people.
The TD-50 (toxic dose 50%) is defined as the dose that is toxic to 50% of the population. TD-50 is often used to indicate responses such as reduced enzyme activity, decrease reproductive success or onset of specific symptoms such as loss of hearing, nausea or slurred speech.
For a particular chemical, there may be a whole family of dose-response curves, illustrated in Figure 2. Which dose is of interest depends on what is being evaluated. For example, for insecticides we may wish to know the dose that will kill 100% of the insects exposed; therefore the LD-95 (the dose that kills 95% of the insects) may be the minimum acceptable level. However, when considering human health and the exposure to a particular toxin, we often want to know the LD-0 which is the maximum dose that does not cause any deaths. For potentially toxic compounds such as insecticides, which may form a residue on food or food additives, we want to ensure that the expected levels of human exposure will have no known toxic effects. From an environmental perspective, this is important because of concerns about increased risk of cancer associated with exposure to toxic agents.
For drug used to treat a particular disease, the efficiency of the drug as a treatment is of paramount importance. In addition to knowing what the therapeutic value (ED-50) is, it is also important to know the relative safety of the drug. For example, there may be an overlap between the therapeutic dose (ED) and the toxic dose (TD) (see Figure 2). That is, the dose that causes a positive therapeutic response in some individuals might be toxic to others. A quantitative measure of the relative safety of a particular drug is the therapeutic index, defined as the ratio of the LD-50 to the ED-50. The greater the therapeutic index, the safer the drug is believed to be. In other words, a drug with a large difference between the lethal and therapeutic dose is safer than one with a smaller difference.
