Guidance Document on Toxicokinetics to accommodate Testing of (Nano)particles

This document provides guidance and considerations around in vivo testing for toxicokinetics of simple-structured, manufactured, poorly soluble and partially soluble spheroidal particles following oral and inhalation exposure. The primary scope is also on inorganic (nano)particles, although some information relevant for organic materials is also included. Experimental designs, analytical methods and reporting requirements are addressed. The document introduces the specific aspects of the toxicokinetics of manufactured (nano)particles that differ in comparison to other chemicals and defines the scope. It also describes the scientific background to relevant topics such as the dissolution rate of poorly soluble and partially soluble (nano)particles, the impact of agglomeration and aggregation status, the exposure route, biotransformation processes and physicochemical properties that influence the toxicokinetics of (nano)particles. The document further provides guidance on the experimental design of repeated oral and inhalation studies to assess the toxicokinetics of (nano)particles, describes a range of analytical methods that can be applied for the detection of (nano)particles or transformation products, and outlines expectations regarding the reporting requirements for experimental conditions related to the animals as well as the analytical aspects of conducting toxicokinetics studies.