Critical elements for human health risk assessment of less than lifetime exposures.

Less than lifetime exposure has confronted risk assessors as to how to interpret the risks for human health in case a chronic health-based limit is exceeded. Intermittent, fluctuating and peak exposures do not match with the basis of the chronic limit values possibly leading to conservative outcomes. This paper presents guidance on how to deal with human risk assessment of less than lifetime exposure. Important steps to be considered are characterization of the human exposure situation, evaluation whether the human less than lifetime exposure scenario corresponds to a non-chronic internal exposure: toxicokinetic and toxicodynamic considerations, and, finally, re-evaluation of the risk assessment. Critical elements for these steps are the mode of action, Haber's rule, and toxicokinetics (ADME) amongst others. Previous work for the endpoints non-genotoxic carcinogenicity and developmental toxicity is included in the guidance. The guidance provides a way to consider the critical elements, without setting default factors to correct for the less than lifetime exposure in risk assessment.