The zebrafish embryo (ZFE) has proven to be a good model to study the toxic effects of chemicals on the neurological system and thus may be a promising model to study behavioral markers of nicotine effects, which may be predictive for addictiveness. We developed a testing protocol to study nicotine tolerance in ZFE using a locomotion test with light-dark transitions as behavioral trigger. Our experiments showed that (1) acute nicotine exposure decreased ZFE activity in response to dark conditions in a dose-dependent fashion; (2) pre-treatment with increasing concentrations dose-dependently reversed the effect of acute nicotine exposure; and (3) a fixed pre-treatment dose of nicotine induced a decreased potency of the acute nicotine exposure. This effect supports the induction of tolerance to nicotine by the pre-treatment, likely through neuroadaptation. This study was recently published in Toxics.

Smoking is characterised by a highly varying, intermittent exposure and the challenge is to choose the most appropriate dose metric. Generally, average daily exposure estimates are used as dose metric, without considering temporal determinants. Using average daily exposure estimates for the smoking scenario can lead to erroneous risk evaluations for several reasons. Inhaled peak air concentrations during a puff can be two to three orders of magnitude higher than the calculated average daily inhaled concentration, which may impact the assessment of both systemic and local health effects. A pragmatic risk assessment is proposed, based on the Margin of Exposure (MoE) approach. The choice of an appropriate dose metric, such as inhaled concentration, inhaled dose or absorbed dose, depends on the type of effect. Temporal characteristics should be considered in the final step of the MoE approach, as is illustrated by two cases, glycerol and benzene.