Overview
CEN ISO/TS 5387:2024 (identical to ISO/TS 5387:2023) provides guidance on lung burden mass measurement of nanomaterials for inhalation toxicity tests. The technical specification explains how to measure nanomaterial mass in respiratory tissues after inhalation exposure to inform on pulmonary deposition, retention, lung clearance behaviour and potential translocation. It complements OECD inhalation test guidance (TG 412 and TG 413) and was approved for provisional application by CEN in 2024.
Key topics and technical requirements
- Scope and definitions: Clarifies nanotechnology terminology (aligned with ISO 80004) including nanoparticle, nanofibre, MMAD and aerosol concepts relevant to inhalation studies.
- Use for risk assessment: Describes how lung burden data support toxicokinetic interpretation and regulatory decision‑making.
- Inhalation exposure and tissue sampling: Guidance on exposure design, selection of lung lobes or whole-lung evaluation, and post‑exposure observation points for measuring retained mass.
- Measurement methods: Overview of available approaches for different material classes (e.g., carbon nanomaterials, metal‑based nanomaterials, polymeric nanomaterials), with considerations for fast‑dissolving versus poorly soluble aerosols.
- Data interpretation and modelling: Procedures to derive clearance kinetic parameters from lung burden data, including at least three measurement time points to evaluate clearance kinetics and application of one‑compartment and two‑compartment first‑order clearance models.
- Annexes: Example test schemes for 28‑day and 90‑day studies (Options A and B) and an informative annex on lung burden measurement methods.
Practical applications
- Supports inhalation toxicity testing for manufactured nanomaterials used in product safety assessments and regulatory submissions.
- Informs toxicokinetic modelling, including lung clearance rates and retention half‑times, to interpret dose–response and persistence in the lung.
- Guides laboratory study design (sampling schedules, tissue processing) to generate defensible lung burden data for risk assessment and hazard classification.
- Helps regulatory bodies and test laboratories harmonize methods when applying OECD TG 412/413 to poorly soluble or retained nanomaterials.
Who should use this standard
- Toxicologists and inhalation study designers
- Contract research organizations (CROs) and analytical laboratories
- Regulatory agencies and risk assessors
- Nanomaterial manufacturers and product safety teams
- Standardization committees and method developers
Related standards and references
- OECD Test Guidelines 412 and 413 (inhalation toxicity for subacute and subchronic studies) - the document is intended to complement these TGs.
- ISO 80004 series (Nanotechnologies - Vocabulary) for consistent terminology.
Keywords: CEN ISO/TS 5387:2024, ISO/TS 5387:2023, nanotechnologies, lung burden, inhalation toxicity tests, nanomaterials, lung clearance, toxicokinetics, OECD TG 412, OECD TG 413.