Toxicological risk assessment – ISO 10993-17 (2023)
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How to Apply ISO 10993 17:2023 — A Practical Guide to Toxicological Risk Assessment (TRA)
ISO 10993‑17:2023 provides a structured approach for evaluating the toxicological risk associated with chemical constituents released from medical devices. The updated standard explains when a Toxicological Risk Assessment (TRA) is required and how to derive safety thresholds that protect patients. The infographic below summarizes the full workflow in an accessible, step‑by‑step format.
1. Start with a clear device description
Every assessment begins with understanding the medical device itself: its materials, intended clinical use, category and duration of body contact, and patient population. These factors determine how conservative the toxicological evaluation must be.
2. Identify and select chemical constituents
Chemical characterization results (per ISO 10993‑18) reveal which constituents need assessment. At this stage, you also determine whether the Toxicological Screening Limit (TSL) can be applied. If the detected total quantity (TQ) is below the relevant TSL, the constituent poses negligible risk and no further evaluation is required. If the TSL cannot be used the exposure should be compared with the analytical evaluation threshold (AET).
3A. Perform hazard assessment
If the constituent exceeds the TSL or is present above the AET, a full hazard assessment is mandatory. This includes checking available toxicological data, identifying the point of departure (NOAEL, LOAEL, BMDL, NIL, etc.), and applying the appropriate safety limit:
- TI (Tolerable Intake) for systemic, reproductive, or developmental endpoints
- CRSD (Cancer risk specific dose) for genotoxic carcinogicity
- TCL (Tolerable Contact Level) for irritation
If no suitable data are available, ISO 10993‑17 allows scientifically justified alternatives, including TTC, (Q)SAR models, or read‑across.
3B. Perform exposure assessment
In parallel to the hazard assessment, exposure estimation determines how much of a constituent a patient could encounter during actual clinical use. ISO 10993‑17 defines four exposure durations (≤1 day, 2–30 days, 31–365 days, >366 days), ensuring assessments reflect actual clinical scenarios. The Estimated Exposure Dose (EEDmax) is calculated using worst‑case assumptions unless release‑kinetics data are available, which allow for more realistic exposure modelling.
4. Calculate the Margin of Safety (MoS)
The Margin of Safety is the heart of the TRA: MoS = Tolerable Level ÷ Estimated Exposure (EEDmax)
A MoS above 1 indicates that exposure is below levels associated with adverse effects, meaning the risk is acceptable. A MoS below 1 requires refinement, additional data, or risk‑control measures.
Why this process matters
This structured approach ensures you evaluate chemical risks consistently, transparently, and in alignment with regulatory expectations. The flow captures the logic of ISO 10993‑17:2023 — starting broad, filtering out low‑risk substances, and focusing effort where it matters most.
Whether you’re preparing a biological evaluation report, supporting regulatory submissions, or improving internal risk processes, understanding this workflow makes compliance more efficient and more robust.
How can Agirad support you?
As experts
in toxicology and ISO compliance, we help manufacturers navigate the evolving
ISO 10993
landscape. We ensure that your Toxicological Risk Assessments are:
- scientifically
sound
- aligned with ISO 10993‑17 and ISO 10993‑18
- well‑documented
for regulatory review
- defensible
and efficient
Whether you
need help interpreting new terminology, applying the TSL approach, or
performing a full TRA, we guide you through every step.