Use of toxicokinetics to support chemical evaluation: Informing high dose selection and study interpretation.

ABSTRACT

Toxicokinetic (TK) information can substantially enhance the value of the data generated from toxicity testing, and is an integral part of pharmaceutical safety assessment. It is less widely used in the chemical, agrochemical and consumer products industries, but recognition of its value is growing, as reflected by increased reference to the use of TK information in new and draft OECD test guidelines. To help promote increased consideration of the important role TK can play in chemical risk assessment, we have gathered practical examples from the peer-reviewed literature, as well as in-house industry data, that highlight opportunities for the use of TK in the selection of dose levels. Use of TK can help to ensure studies are designed to be of most relevance to assessing potential risk in humans, and avoid the use of excessively high doses that could result in unnecessary suffering in experimental animals. Greater emphasis on the potential contribution of TK in guiding study design and interpretation should be incorporated in regulatory data requirements and associated guidance.