Acute subcutaneous systemic toxicity test. EN ISO 10993-11: 2018 - Biological evaluation of medical devices. Test for systemic toxicity by subcutaneous exposure. 

Test with the Certificate of Good Laboratory Practices (GLPs).

The release of chemical components from a medical device in the body can cause systemic toxicity. The acute systemic toxicity test is designed to provide evidence of the existence of systemic adverse effects. Subcutaneous systemic toxicity tests are suitable for medical devices in contact with a subcutaneous environment leading to the release of leachable chemicals. For the evaluation, the liquid medical device or extracts of the product obtained with polar solvents (physiological saline solution, 5% hydroalcoholic solution, water) or non-polar solvents (vegetable oil) are used, with their corresponding solvent controls without having been exposed to the product.

To carry out the test, groups of 5 rodents (mice or rats) are used, which are inoculated subcutaneously, with a single dose of the medical device, or each of the extracts, and their corresponding controls. Repeated doses can also be given over a 24-hour period. The maximum allowed inoculation volume is 20 mL/kg for rats and 50 mL/kg for mice. The rodents are observed daily for three days. The test is considered negative if none of the animals inoculated with the product extract show a significantly greater biological reaction than that observed in animals inoculated as controls with the solvent used to prepare the device extract. If two or more of the inoculated rodents die, or show signs of toxicity (clinical observation), or three or more of the rodents lose more than 10% weight, the tested product does not meet the test requirements. If the animals only show signs of a slight biological reaction, and no more than one animal shows significant signs of a biological reaction or dies, the test should be repeated with groups of 10 rodents.