Systemic Responses to Exposure to Chemicals and Their Responses as Indicators

Along with physico-chemical properties and the potential to elicit biological activity, the three routes of exposure (inhalation, contact, and ingestion) and the corresponding three portals of entry (the respiratory system, the skin, and the digestive system) determine to a large extent the fate and disposition of xenobiotics in the body (Hayes, 1984). Whatever the port of entry or the main target organ for attack, toxic chemical exposures induce an overall systemic response that is the integrated outcome of multifunctional involvement (Cralley and Cralley, 1985). Qualitative and quantitative evaluation of systemic effects also lead to opportunities to explore biochemical mechanisms of toxicity to obtain a greater understanding of biotransformation. Evaluation of systemic effects is necessary to assess the role of defence mechanisms, if any, employed by an organism against external toxic insult. These factors could prove of assistance in the assessment of risks from chemicals, provided the methods used for evaluating systemic effects are precise and adequately validated under different sets of exposure conditions (Klassen et aI., 1986). The target organ affected is of paramount importance in understanding mechanisms of toxicity. Useful indications that a specific organ is the target of a toxic episode can be obtained from exploratory clinical examination. The effects must necessarily be dose-related to qualify as biological indicators of exposure. Critical local concentrations have to be attained to elicit adverse responses at cellular, tissue, or functional levels (Hodgson and Guthrie, 1980). Thus, three WHO reports embody the principles to evaluate toxicity, provide guidelines for epidemiological studies on the health effects of environmental chemicals, and describe the special situation of prenatal exposures; they may be considered overviews of the methodological problems with linking exposure to effects observed in humans and in experimental animals (WHO, 1978, 1983, 1984). Methods to assess the effects of chemicals on reproductive functions have also been reviewed in SCOPE 20, SGOMSEC 1 report (Vouk