When this test applies
ISO 10993-1:2025 flags systemic toxicity for devices with prolonged (24 h to 30 days) or long-term (over 30 days) body contact. Acute systemic injection answers the single-exposure question; repeated dose answers the cumulative one. The 14-day study is the subacute tier — the shortest repeated-dose design ISO 10993-11 recognises — and it is the usual choice where clinical contact is prolonged rather than permanent.
When to run it
Late. Cytotoxicity, sensitization and irritation should be clear first, and the material and its manufacturing process must be locked, because a formulation change invalidates the study. Run chemical characterisation before you commission this: where the extractables profile is well characterised and the margins are wide, an ISO 10993-17 toxicological risk assessment can sometimes address the systemic endpoint without an animal study, and that decision is much cheaper to make before the 8 to 10 weeks are spent.
What a pass tells you
That across 14 consecutive days of dosing there were no toxicologically significant differences between the test and control groups in clinical signs, body weight, food consumption, clinical pathology, organ weights or histopathology — assessed per ISO 10993-11.
What it does not tell you
Nothing about longer exposure. A clear 14-day result does not stand in for the 28-day study where contact duration warrants it, and it says nothing about chronic effects. It also says nothing about local tissue response, genotoxicity or sensitization, each of which is a separate endpoint with its own study.
Method
Testing per ISO 10993-11:2017. Two extracts are prepared, one polar and one non-polar, at 18 mL per extract, giving at least 28 discrete dose portions — enough for one dose of each extract on each of the 14 days. Extraction ratio follows ISO 10993-12: 6 cm²/mL for material under 0.5 mm thick, 3 cm²/mL at 0.5 mm or thicker, or 0.1 to 0.2 g/mL where surface area is indeterminate. Dosing is by systemic injection in the rat (preferred) or mouse, daily for 14 days, followed by terminal clinical pathology, organ weights and histopathology against a concurrent control group.
Where it runs
This method is internationally sourced. The laboratory is ISO/IEC 17025 accredited and GLP certified, and the report is issued under Groenakker cover, in Groenakker’s report template or in your document template on request at no extra cost. Turnaround is 8 to 10 weeks.
Usually ordered alongside
Acute systemic injection (GRK-4004-02) where the single-exposure endpoint is also open, and material-mediated pyrogenicity (GRK-4004-01), which is a distinct endpoint rather than a subset of this one. Chemical characterisation and an ISO 10993-17 assessment normally precede it and can change whether it is needed at all. Where contact duration is long-term, the 28-day dual-route study (GRK-4004-04) is the tier above this one.
