Overview
ISO/TR 22019:2019 - Nanotechnologies - Considerations for performing toxicokinetic studies with nanomaterials is a technical report from ISO/TC 229 (2019) that reviews the background, principles and practical issues for performing toxicokinetic (ADME) studies on nanomaterials. The document clarifies why nanomaterials (NMs) require specific toxicokinetic consideration - their particulate nature, size-dependent behavior and surface chemistry mean absorption, distribution, metabolism and excretion (ADME) can differ substantially from dissolved chemicals or bulk particles. Annex A reproduces terminology used in OECD TG 417:2010 and Annex B summarizes quantitation methods.
Key topics and technical requirements
The report focuses on practical guidance rather than prescriptive test procedures. Major topics include:
- Importance for risk assessment: how toxicokinetic data link external exposure to internal dose and support target-organ identification, grouping/read-across and persistence assessment.
- Factors influencing toxicokinetics: dissolution rate, particle size, shape, surface chemistry, agglomeration/agglomeration and protein corona formation.
- Analytical challenges: detection and quantitation of elemental, radiolabelled or fluorescent labels, particle versus dissolved fraction measurement, and limits of detection.
- Dosing considerations: relevant exposure routes, dose metrics (mass, particle number, surface area) and realistic exposure conditions.
- Absorption by route: skin, gastrointestinal and respiratory uptake considerations specific to NMs.
- Distribution and transport: organ distribution, macrophage-mediated transport, potential translocation across placenta and blood–brain barrier (BBB).
- Metabolism/degradation and excretion: issues around persistence, bioaccumulation and pathways for elimination.
- Modeling implications: the need to adapt physiologically based pharmacokinetic (PBPK) approaches for particulate behaviors.
Practical applications and users
ISO/TR 22019:2019 is intended for professionals involved with:
- Regulatory risk assessment and safety dossiers for nanomaterials
- Toxicologists and study designers planning ADME/toxicokinetic studies for NMs
- Nanomaterials manufacturers and formulators seeking read-across or grouping justification
- Academic researchers and laboratories developing analytical and PBPK methods for nanoparticles
- Nanomedicine developers needing guidance on systemic distribution and persistence
The report helps users design meaningful toxicokinetic studies, select appropriate dose metrics and analytical approaches, and interpret internal exposure data for safety decision-making.
Related standards and guidance
- OECD Test Guideline 417 (Toxicokinetics) - terminology and context (not intended for NMs)
- ISO 10993-16:2017 - toxicokinetic study design for medical-device leachables
- ICH S3A / S3B, EMA and FDA PBPK guidance - referenced for modeling approaches but not fully applicable to NMs
Keywords: ISO/TR 22019:2019, nanotechnologies, toxicokinetic studies, nanomaterials, ADME, PBPK, OECD TG 417, nanoparticle toxicokinetics.