Subacute systemic toxicity test by topical/dermal route with medical devices (ISO 10993-11: 2017).
Test with the Certificate of Good Laboratory Practices (GLPs).
The animal species chosen for the test are New Zealand albino rabbits and Wistar rats of known origin and with a defined microbiological health status. According to the ISO 10993-11 standard, a total of 6 animals for rabbits (3 from each sex) or 10 animals for rodents (5 for each sex) must be administered with the test product and 6 or 10 animals with the control product. Testing in a single sex is acceptable when the device is intended for use in only one sex.
The material must be manufactured, processed, remove contaminants and sterilized by the method provided for the final product, confirmed with adequate documentation to be attached to the material. Due to the duration of the tests, they must be prepared in such a way as to ensure their stability.
The client must indicate the dosage and frequency of application for the test product. Control animals will be dosed with equal volume and frequency with physiological saline solution or the extraction media when the extract of a medical device is analysed. The client can also request to use an authorised product with similar properties to the test product as the negative control. In this case, the client must provide us with the control product. Dosing in our laboratory can be done 5 days a week (product is not dosed on weekends or public holidays).
The duration of the test for subacute topical/dermal toxicity is between 24 hours and 28 days. The selection of time intervals between 14 days and 28 days is consistent with most international regulatory guidelines and considered a reasonable approach.
During the duration of the study, the test animals will be monitored as indicated below:
- Blood analysis 48 hours before administration of the product
- Blood and urine analysis before humane slaughter of the animal.
- Measurement of the body weight of the animals 24 hours before the application of the product and then every week of observation.
- Observation and clinical signs of the animals (daily), including changes in the skin and coat, eyes and mucous membranes, respiratory, circulatory, vegetative and nervous systems, somatomotor and behavioral activity.
- After humanitarian sacrifice:
- Complete macroscopic autopsy.
- Extraction of organs for histopathological evaluation. The client must select the study organs. The ISO 10993-11 standard indicates a list for reduced histopathology for tests with medical devices with composition of common use. This list includes the following organs: heart, liver, adrenal glands, kidneys, skin, spleen, muscle, brain, ovaries, lungs and bronchial samples, bone (femur or sternum), bone marrow (from femur, rib or sternum).