Use of Toxicokinetics in Hazard Assessment

Data on absorption provides important knowledge for the hazard assessment. If a substance is not absorbed or poorly absorbed, it is not surprising that toxicity studies show no or only weak effects. Therefore, in the hazard assessment it should be taken into consideration that a lack of effects in toxicity studies could be caused by nonabsorption of the substance rather than lack of toxicity. 

First pass metabolism (metabohsm in the intestinal wall or by the fiver before the substance reaches the systemic circulation) can also be a cause for nontoxicity, which can be route- and species-dependent. Information about which metabohtes, and the relative quantities thereof, are formed, is important. Chemical substances are metabohzed to metabohtes, which may be toxicol-ogically more or less active than the parent compound, and the relative quantity of the metabolites may differ greatly among animal species. If it is known that toxicity is related to formation of an active metabolite, knowledge about the amount of this particular metabolite in humans and test animals is very important for the hazard assessment. If humans do not form the toxic metabohte, the hazard can be considered limited and vice versa. 

Data on distribution give an indication of whether a particular tissue may be exposed to the substance or not. The extent of chemical distribution into tissues depends on the extent of plasma protein and tissue binding and this may vary among species. This is also the case for passage of chemicals into the brain, which is protected by the blood-brain barrier. 

Data on excretion could indicate a possible hazard, e.g., to the breastfeeding infant, if the substance is excreted into breast rmlk. 

The elimination half-life of the substance gives important information about the duration of internal exposure following an episode of exposure. The half-hfe (half-time, Ty ) is the time taken for the concentration of a substance in the blood, tissue/organ, or whole body to decline to half of its original value. 

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