Toxicity local versus systemic

Local versus systemic toxicity Local effects refer to those that occur at the site of first contact between the biological system and the toxicant systemic effects are those that are elicited after... 

Hazard identification is the step in the risk assessment that qualitatively characterizes the inherent toxicity of a chemical. Scientific data are evaluated to establish a possible causal relationship between the occurrence of adverse health effects and chemical exposure. This step includes characterization of acute, subchronic, and chronic effects the potential for local versus systemic effects the influence of the route of exposure the relevance, to humans, of effects seen in animals an evaluation of the biological importance of the observed effects the likelihood of the effects occurring under certain conditions and the potential implications for public health. This step should be based on a thorough review of all the data that may provide information that is relevant to evaluating the potential chemical hazard. This may include data describing the effects on a variety of test animals, in vitro studies that characterize mechanisms of toxicity, metabolism, physiologically based pharmacokinetic studies, structure-activity relationships, short-term human studies, and epidemiological studies. Animal studies may focus on particular types of effects and may include reproductive toxicity studies,... 

As a general rule the NOEL/NOAEL is a dose from a controlled animal experiment where no adverse effect (i.e., an effect not considered harmful) is noted. The experiment does not establish that no effect can possibly occur at that dose under any conditions - it only denotes that none of the effects looked for in the experiment was observed. Since a statistical significance test is typically used to establish whether or not an effect occurred, the NOEL/ NOAEL will tend to diminish as the sensitivity of the measurement or the number of observations increases. Since the burden of proof is on science to show that an effect has occurred, greater uncertainty tends to raise the level of exposure that is deemed accept-able/tolerable. The selection of the effect that is considered adverse is a matter of societal values (i.e., localized, reversible, mild discomfort versus frank, irreversible systemic toxicity). That is, establishing that an effect has occurred is a separate consideration from how much one cares if it will occur or not. 

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