Acute Systemic Toxicity test. UNE-EN ISO 10993-11: 2018. Biological evaluation of medical devices.
Test Accredited by ENAC (Spanish National Accreditation Entity).
Test with the Certificate of Good Laboratory Practices (GLPs).
The chemical components removed from a medical device in the body can cause systemic toxicity. The acute systemic toxicity test is designed to provide evidence of systemic adverse effects occurring within 72 hours after single, multiple or continuous exposure of a test sample for 24 hours.
Medical devices or their leachable substances can enter the body through multiple routes of exposure. The route of exposure in the test should be that which is most clinically relevant to the use of the device, eg, dermal, intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous, or oral administration.
The animals used for the evaluation of acute systemic toxicity are young adult rodents. Groups of 5 rodents (rats or mice) are used, which are administered with the medical device (for liquid or soluble solid products) or with extracts of the medical device (in the case of non-soluble solid products) obtained with polar solvents (physiological saline solution) and non-polar (vegetable oil), and their corresponding controls. When the intended use of a medical device is for only one sex, testing should be performed on animals of only that sex. Animals receive a single sample dose or, if necessary, multiple dose fractions for a maximum period of 24 hours. The client must choose the time and frequency of application, according to the intended use of the medical device.
It should be noted that the ISO 10993-11 standard indicates, for mice, a maximum single dosage volume of 50 mL/Kg subcutaneously, 2 mL/Kg intramuscularly, 50 mL/Kg intraperitoneally, 50 mL/Kg by gavage, and 50 mL/Kg intravenously; while for rats, the standard indicates a maximum single dosage volume of 20 mL/Kg subcutaneously, 1 mL/Kg intramuscularly, 20 mL/Kg intraperitoneally, 50 mL/Kg by gavage, and 40 mL/Kg intravenously. It should also be considered that for intramuscular inoculation, it should not exceed 0.1 mL per inoculation site for mice and 0.2 mL per inoculation site for rats.
After the administration of the medical device or its extracts, the animals are observed daily for three days, in which the appearance of side effects is studied: adverse clinical signs, change in body mass, serious pathological findings and/or death of the test subjects. The frequency and duration of the observations can be adjusted depending on the nature and severity of the toxic reactions and the recovery time.
The medical device is considered to pass the test if none of the test animals show a biological reaction significantly greater than that observed in the control animals. If two or more of the five test animals die, or show signs of toxicity (clinical observation), or three or more of the animals lose more than 10% of their body weight, the tested product does not meet the test requirements. If one of the animals inoculated with the product shows signs of a slight biological reaction, or one of the animals shows significant signs of a biological reaction or dies, the test should be repeated with groups of 10 rodents. If in the repeat test with 10 rodents none show signs of significant biological reactivity, compared to the respective controls, the test product meets the requirements of the test.