Intracutaneous Reactivity Test ISO 10993

What Is the Intracutaneous Reactivity Test?

Medical devices may contain various cheMICal substances, including additives like lubricants, colorants, adhesives, and sterilization residues. These substances coULd potentially cause irritation, which may manifest as inflammation, REDness, swelling, heat, and pain. Therefore, irritation testing is essential to assess whether a medical device may trigger such reactions upon contact with the human body.

Irritation testing methods include intracutaneous reactivity, skin irritation, eye irritation, and mucosal irritation tests. For devices not intended for direct contact with the eyes, skin, or mucosa—such as implants or externally communicating devices—the intracutaneous reactivity testis recommended. This in vivomethod evaluates irritation potential by injecting extracts of the medical device into the dermis of test animals.

I. Purpose of the Test

To assess the risk of skin contact hazards caused by chemicals released from medical devices.

II. Test Method

Test Subject: Rabbits

Extraction Media:

Polar: 0.9% sodium chloride solution

Non-polar: sesame oil

Injection Procedure:

Each extract is injected into five different siteson one side of the back of three animals, 0.2 ml per site.

The corresponding control media are injected into five sites on the opposite side.

Site layout is standardized (see description below).

Observation Times:

Immediately after injection

At 24, 48, and 72 hours post-injection

Evaluation Criteria:

Erythema (Redness):

0: No erythema

1: Very slight (barely visible)

2: Clearly visible

3: Moderate

4: Severe or eschar formation preventing grading

Edema (Swelling):

0: No edema

1: Very slight (barely visible)

2: Clearly visible, with raised edges

3: Moderate (raised about 1 mm)

4: Severe (raised over 1 mm and extending beyond the area)

Maximum Possible Score per Site: 8

Other Observations:

Any abnormal reactions at injection sites should be recorded and reported.

Injection Site Layout

1– Head end

2– Polar extract injection (0.2 ml)

3– Non-polar extract injection (0.2 ml)

4– Polar control injection (0.2 ml)

5– Non-polar control injection (0.2 ml)

6– Tail end

III. Result Evaluation

The final result is based on statistical analysis of the erythema and edema scores.

A mean score ≤ 1.0indicates that the sample meets the test requirements.

IV. Relevant Standards

1. iso 10993-10:2010 – Biological evaluation of medical devices – Part 10: Tests for irritation and skin sensitization

2. GB/T 16886.10-2017 – Biological evaluation of medical devices – Part 10: Tests for irritation and skin sensitization

3. GB/T 14233.2-2005 – Test methods for infusion, transfusion, and injection equipment for medical use – Part 2: Biological test methods

4. GB/T 16175-2008 – Biological evaluation methods for medical-grade silicone materials

5. EN ISO 10993-10:2010 – Biological evaluation of medical devices – Part 10: Tests for irritation and skin sensitization

6. ISO 7405:2018 – Dentistry — Evaluation of biocompatibility of medical devices used in dentistry