ABSTRACT

The discussion of effects of chemicals as a result of exposure to a particular dose necessarily must be followed by a discussion of the path by which that dose elicits that response. The response depends on the quantity of chemical exposure or administration within a given time period. Two types of dose–response relationships exist, depending on the number of subjects and doses tested. Except for lethality, the selection of a measurable or observable endpoint is crucial. A desirable biomarker may be one that accurately reflects the presence of the chemical at the molecular site or suggests that the toxic effect originates from the target organ. The selection of a measurable endpoint thus depends on the suspected mechanism of toxicity, if known, or on empirical determinations based on the chemical formula. Some biomarkers are also subjective, such as reliance on histological grading or calculation of the degree of anesthesia, pain, motor activity, or behavioral change.