Table 2.

Principles of toxicology

Principle	Explanation
The relationship between dose and effect is an important feature, with an expectation of linearity or monotonicity. This is sometimes described using the maxim, “the dose makes the poison”.	The toxicological response that is observed is expected to be associated with the amount of exposure, with a monotonic relationship between these two factors. The effect that is examined can be quantal, such as life/death, or continuous, such as organ weight. Further, effects can be characterized as acute (rapidly developing), subacute (less severe than acute), or chronic (progressing at a slow and varying rate). Because a monotonic relationship is assumed across the entire dose range, extrapolation from high to low doses (or vice versa) is possible.
Exposures should be characterized based on duration, exposure route, and developmental stage. .	Exposures can be separated based on duration (acute, subacute, subchronic, and chronic). They also can be distinguished based on the route of exposure (oral, intravenous, intramuscular, dermal, inhalatory, subcutaneous). They are also sometimes considered separately if exposures occur during development versus in adulthood. These factors can influence the severity and type of the effects observed.
Compounds are studied and understood based on their absorption, distribution in the body, metabolism, and excretion from the body (ADME).	ADME can be influenced by the physiological state of the individual (i.e. young individuals with diminished metabolic capacities) and the physiochemical properties of the compound (i.e. lipophilic versus hydrophilic substances). Metabolism is a process to enhance the removal of compounds from the body (e.g. by changing its water solubility), not necessarily a process that makes chemicals less toxic.
Toxicants can induce general or tissue-specific effects.	Although some toxicants induce general toxic effects, many induce effects that are tissue- and organ-specific. Some of this specificity can be based on the route of exposure (i.e. the lungs are the entry-point for inhalatory exposures), the chemical’s accumulation in a specific tissue, the presence of enzymes in specific organs that metabolize a compound to a more active form, the presence of specific receptors in a tissue or organ, and other factors including physiological sensitivities.