Acute Eye Irritation Test

What Does "Acute Eye Irritation Test" Mean for a Medical Device?

The acute eye irritation test determines whether a material or its extract, when it contacts ocular and mucosal tissue, produces reversible inflammatory change (irritation) or irreversible tissue damage (corrosion). For a medical device the test is performed under the biological-evaluation framework ISO 10993-23:2021 (Tests for irritation), which in China is the current national standard GB/T 16886.23-2023 (医疗器械生物学评价 第23部分:刺激试验, identical adoption of ISO 10993-23:2021, effective 2024-12-01) — not the older ISO 10993-10 / GB/T 16886.10. This standard-system change is the single most important thing to get right on a test request, and many legacy documents still cite the old numbers. For chemicals and cosmetics the parallel framework is OECD TG 405 (in vivo acute eye irritation/corrosion) and its validated in-vitro replacements (OECD 437 BCOP, 438 ICE, 491 STE, 492/492B RhCE, 496 Ocular Irritection). The medical-device and chemical frameworks share the same biology but differ in sample preparation (device extract vs neat chemical), species priority and the role of the rabbit in vivo test, so the test report must name which framework applies.

Why the Standard Number Changed — and Why It Matters

In 2021 the ISO 10993 series reorganised its irritation content, and China's GB/T 16886 followed in 2023–2024:

• ISO 10993-10:2021 (China GB/T 16886.10-2024) was renamed Tests for skin sensitisation and all irritation content — skin, eye, mucosal — was removed.
• ISO 10993-23:2021 (China GB/T 16886.23-2023, effective 2024-12-01) is the new, current standard for irritation, including the eye irritation test, plus updated in-silico and in-vitro pre-considerations.

The practical consequence: a test request that still cites "GB/T 16886.10-2017" for an eye irritation test is citing a withdrawn standard, and a regulatory submission built on it is out of date. The correct citation for a medical-device eye irritation test today is GB/T 16886.23-2023 / ISO 10993-23:2021, with sample preparation per GB/T 16886.12-2023 / ISO 10993-12:2021. Sample preparation matters because devices are not applied neat — they are extracted in polar (water/saline) and non-polar (vegetable oil) vehicles, and the extract is what is dosed to the eye, which is why the medical-device test is structured very differently from a chemical Draize test.

How Is the In-Vivo Eye Irritation Test Performed?

Where in-vivo testing is justified after a weight-of-evidence analysis, the test follows the same Draize-derived principle across the device and chemical frameworks: a single dose is applied to one eye of an albino rabbit, the untreated eye serves as the control, and the ocular response is scored at defined intervals to assess severity and reversibility. The OECD 405 procedure (and the device equivalent) is:

• Species — albino rabbit, the preferred model; healthy young adults, both eyes examined within 24 h pre-test for pre-existing irritation.
• Dose — liquids 0.1 mL; solids/pastes ≤ 100 mg or 0.1 mL (gently compacted); aerosols collected and dosed, or burst-sprayed at 10 cm. For devices, the extract (polar and non-polar, per ISO 10993-12) is dosed at 0.1 mL.
• Application — into the conjunctival sac after pulling the lower lid; lids held ~1 s to prevent loss; eye not washed for ≥ 24 h (except solids at 1 h).
• Anaesthesia/analgesia (OECD 405, mandatory since 2017) — buprenorphine 0.01 mg/kg SC 60 min pre-dose, proparacaine/tetracaine topical 5 min pre-dose, then buprenorphine + meloxicam post-dose on a scheduled regime. This avoids most pain without affecting the ocular response.
• Scoring — at 1, 24, 48, 72 h, then 7/14/21 days; fluorescein staining and slit-lamp biomicroscopy routinely used.
• Animals — initial test in one animal; if not corrosive/severe, confirm in up to two more, sequentially. Device tests typically use ≥ 3 animals.
• Reversibility — observed up to 21 days; humane endpoints (corneal perforation, grade-4 opacity, limbus destruction > 50 %, purulent infection) trigger early euthanasia.

The Draize scoring (Table 1 of OECD 405) grades four tissues on ordinal scales — cornea opacity (0–4), iris (0–2), conjunctival redness (0–3), chemosis (0–4) — and the report is the full time-course of these scores plus a narrative description, not a single number.

What Are the In-Vitro Alternatives — and Which Apply to Devices?

A decade of validation has produced six OECD-adopted in-vitro/ex-vivo methods that replace or reduce the in-vivo test for chemicals, and the medical-device standard now explicitly considers in-silico and in-vitro pre-screens before any animal test:

The key device caveat: these methods were validated on neat chemicals, and the medical-device standard (GB/T 16886.23) notes that in-vitro irritation methods are confirmed only for pure chemicals, not for device extracts — so for devices the in-vivo rabbit test remains the reference method, with in-vitro BCOP/RhCE used as pre-screens or where justified. A test report should state which method was used and why, not assume "in-vitro replaces in-vivo" for every device.

How Are Device Extracts Prepared — and Why Polar + Non-Polar?

Unlike chemicals, a medical device is not dosed neat. Per ISO 10993-12 / GB/T 16886.12, the device (or a representative sample, surface-area-to-volume ratio typically 6 cm²/mL for flat materials, or 0.2 g/mL for irregular forms) is extracted in two vehicles:

• Polar extract — saline or water, the relevant physiological vehicle.
• Non-polar extract — vegetable oil (or, where justified, another non-polar vehicle).

Both extracts are dosed to separate animals/groups, because device leachables partition differently between polar and non-polar media — a plasticiser that is harmless in saline may leach into vegetable oil and irritate. This dual-extract design is the single biggest structural difference between the medical-device eye irritation test and the chemical Draize test, and it is why a device test costs and takes longer than a chemical test.

What Does the Test Report Need to Contain?

For a medical-device eye irritation test under GB/T 16886.23-2023 / ISO 10993-23:2021, the report must include:

• Correct standard citation — GB/T 16886.23-2023 / ISO 10993-23:2021 (not the withdrawn -10/-2017).
• Sample preparation — device description, surface area, extraction vehicle(s) (polar + non-polar), extraction conditions (time/temperature per ISO 10993-12), extract concentration.
• Test system — species/strain, number/sex, age, source, acclimatisation, housing.
• In-vitro pre-screen (if any) — method (BCOP/RhCE), result, and the weight-of-evidence justification for any in-vivo step.
• Anaesthesia/analgesia regime — if in-vivo, the full pre- and post-dose schedule (OECD 405 / device equivalent).
• Draize scores — the full time-course table (cornea/iris/conjunctivae/chemosis at each time point), per animal, plus a narrative.
• Conclusion — irritant / non-irritant / corrosive, reversibility, and the classification (Cat 1 / Cat 2 / non-classified under UN GHS where applicable).

For the skin side of the irritation family, see our Skin corrosion/irritation test, and for the overarching biocompatibility framework, biocompatibility testing to ISO 10993.

FAQ

Which standard governs the acute eye irritation test for a medical device?
GB/T 16886.23-2023 / ISO 10993-23:2021 (Tests for irritation), effective 2024-12-01. This replaced the irritation content previously in GB/T 16886.10-2017 / ISO 10993-10, which has been withdrawn for irritation (GB/T 16886.10-2024 now covers only skin sensitisation). A submission still citing GB/T 16886.10-2017 for an eye irritation test is out of date.

Can in-vitro methods (BCOP, RhCE) replace the rabbit test for medical devices?
Partially. The validated in-vitro methods (OECD 437 BCOP, 492 RhCE, etc.) were validated on neat chemicals, and GB/T 16886.23 notes they are confirmed for pure chemicals, not device extracts. BCOP and RhCE are used as pre-screens and for screening device extracts, but the in-vivo rabbit test remains the reference method for device-extract eye irritation where in-vitro data are insufficient.

Why is a device eye irritation test dosed with extract, not the device itself?
Because devices are solid and cannot be placed in the conjunctival sac. Per ISO 10993-12, the device is extracted in polar (saline) and non-polar (vegetable oil) vehicles, and the extracts are dosed separately, because leachables partition differently between vehicles. This dual-extract design is the main structural difference from the chemical Draize test.

What is the Draize scoring system?
A four-tissue ordinal scale (OECD 405 Table 1): corneal opacity (0–4), iris (0–2), conjunctival redness (0–3), chemosa (0–4), scored at 1/24/48/72 h and 7/14/21 days. The report is the full time-course plus a narrative, not a single number; reversibility within 21 days distinguishes irritant (reversible) from corrosive/severe (irreversible).

How many animals does the test use?
The in-vivo test starts with one animal (chemical framework) or typically ≥ 3 animals (device framework), with sequential confirmation. OECD 405 mandates topical anaesthesia and systemic analgesia, and humane endpoints (corneal perforation, grade-4 opacity, limbus destruction > 50 %, purulent infection) trigger early euthanasia, so the test is conducted only where in-vitro and weight-of-evidence data are insufficient.

Our Testing Capabilities

As an ISO/IEC 17025-accredited third-party laboratory, Beijing ZKGX Research provides acute eye irritation testing for medical devices and materials aligned to the current framework:

• In-vivo eye irritation to GB/T 16886.23-2023 / ISO 10993-23:2021, with dual-vehicle extract preparation (polar saline + non-polar vegetable oil) per GB/T 16886.12-2023 / ISO 10993-12:2021, Draize scoring time-course (1/24/48/72 h, 7/14/21 d), fluorescein + slit-lamp, OECD-405 anaesthesia/analgesia regime and humane endpoints.
• In-vitro pre-screen / screening — BCOP (OECD 437) and RhCE / EIT (OECD 492) on device extracts and raw materials, as part of the weight-of-evidence approach before any in-vivo step.
• Standard-system correctness — we cite the current GB/T 16886.23-2023 / ISO 10993-23:2021, and flag legacy GB/T 16886.10-2017 citations for update before testing.
• Chemical / cosmetic testing — OECD 405 in-vivo and the OECD 437/438/491/492/492B/496 in-vitro battery for GHS classification.
• Integrated biocompatibility — eye irritation alongside skin irritation (ISO 10993-23), skin sensitisation (GB/T 16886.10-2024) and cytotoxicity, as part of a full ISO 10993 biological-evaluation programme.

Sample types include medical-device materials and finished devices (extracts), contact-lens care products, topical/intravaginal/ophthalmic formulations, cosmetics, and industrial chemicals. If you have a specific product type, target market (China NMPA / EU MDR / US FDA), or regulatory framework (GB / ISO / OECD), contact the laboratory to confirm the correct standard, sample-preparation method, and reporting format before testing.