Site of action

Various target organs may be involved in the immune response, but this usually depends on the type of reaction rather than on the distribution of the foreign substance. The many substances which cause immune responses may cause anaphylactic reactions giving rise to asthma and various other symptoms as described above. The site of exposure to the foreign compound may not necessarily be the lungs, however. Similarly, a common immune response is urticaria, or the formation of wheals on the skin which can occur when exposure has been via the oral route. Thus, the target organ is generally due to the particular response rather than the circumstances of exposure or distribution of the compound. However, there are exceptions to this such as the type IV cell-mediated immune reactions where the cell is altered by the foreign compound and is then a target. In the case of halothane hepatitis the liver is the target for metabolic reasons (see Chapter 7 for more detail). Another exception is the situation where the foreign compound is chemically reactive and reacts with proteins in the skin or respiratory system. These altered proteins may then become targets for an immune response at the site of exposure, although there may well be other sites involved as well. Thus the final response is determined by the type of immune mechanism involved.

Thus, immune-mediated responses can be immediate or delayed, localized or widespread. The response can be restricted to the area of exposure or can be systemic. Similar compounds may cross-react or produce very different responses. Many different foreign compounds can cause an immunotoxic response: drugs such as penicillin, halothane and hydralazine, industrial chemicals such as trimellitic anhydride and toluene diisocyanate, natural chemicals such as pentadecylcatechol found in poison ivy, food additives such as tartazine and food constituents such as egg white (albumen). However, these may not be immunotoxic in all exposed individuals, and sometimes chemically similar compounds are not immunotoxic. Also, some highly reactive compounds and reactive metabolites of compounds such as paracetamol (see Chapter 7) do not seem to be immunotoxic despite reacting with protein. These are currently areas of obscurity in immunotoxicology, but the importance of this aspect of toxicology is increasing in view of the growing realization that possibly many adverse effects in humans are mediated by the immune system.

6.6 Genetic toxicity

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