Toxicokinetic analysis identifies the level of drug exposure which elicits an adverse event in animals. Consideration of toxicokinetics is an integral part of the safety assessment process for pharmaceuticals, helping to inform study design and assess potential risks in humans. However, it is much less widely used in the evaluation of non-pharmaceutical chemicals. With support from an expert working group, we organised a cross-sector workshop on 'Toxicokinetics and the 3Rs' in 2008 to consider:
The potential application of toxicokinetic information in chemical hazard identification and characterisation and its role in chemical risk assessment;
The 3Rs implications of such an application of toxicokinetic information;
Potential refinement, reduction and replacement methodologies for the generation of toxicokinetic information.
A review paper was published based on the discussions at the workshop. The working group produced a follow up paper using practical examples from the agrochemical industry to highlight how toxicokinetics can provide value in dose selection and study interpretation, while also reducing and refining animal use.
Creton S et al. (2009) Application of toxicokinetics to improve chemical risk assessment: Implications for the use of animals. Regulatory Toxicology and Pharmacology 55: 291-299 doi: 10.1016/j.yrtph.2009.08.001
Creton S et al. (2011) Use of toxicokinetics to support chemical evaluation: Informing high dose selection and study interpretation. Regulatory Toxicology and Pharmacology 62: 241-247 doi: 10.1016/j.yrtph.2011.12.005