Category: Toxicology & Biocompatibility

Raw material characterization ISO 10993-12, ISO 10993-18, USP

Cytotoxicity ISO 10993-5, USP 87

Cytotoxicity is a rapid, standardized test that is very sensitive and is an inexpensive way to determine if the materials in that of a medical device contain significant quantities of harmful extractables and their effect on cellular components.  Required for all types of medical devices. Cellular toxicity is covered in ISO 10993-5. For agar overlay media is placed on top of a monolayer of L-929 cells, and a sample is placed on top of the agar media then incubated. For MEM elution the sample is place in contact with the monolayer of L-929 cells and then incubated.  In both methods the cells are scored for cytopathic effect.

Genotoxicity ISO 10993-3

Genotoxicity uses cell cultures, usually mammalian to determine gene mutations, change in chromosome structure and number, and other gene toxicities caused by medical devices, material or their extracts.  This is described in ISO 10993-3.

Hemocompatibility, Hemolysis ASTM, NIH, ISO 10993-4

Hemocompatibilitly test for compatibility for all devices that come in contact with circulating blood, either directly or indirectly. Depending on the type of contact the device has with blood and clinical concerns determines the type of hemocompatibility that is suggested by ISO 10993-4.

Sensitization ISO 10993

Sensitization or hypersensitivity tests for adverse reactions in animals by exposing the skin to the material or taking extracts from the device or materials and injecting and/or topically applying them to the animal. Sensitization reactions are noted by observing redness and swelling as it interacts with the body's immune system.  This is outlined in ISO 10993-10.

Irritation tests ISO 10993

Irritation tests the reaction to a single, repeated or continual exposure from device materials that may produce skin, mucosal, or eye irritation- a local tissue response characterization by the usual signs of inflammation- redness, and swelling, and could be accompanied by heat and pain.  Different from sensitization in that it is without the involvement of an immunological mechanism.  This is outlined in 10993-10.

Systemic toxicity ISO 10993

Systemic Toxicity (acute) evaluates the potential adverse effects of medical devices on the body's organs and tissues that are remote form the site of contact. Depending on the type of device being tested topical, inhalation, intravenous, intra peritoneal, or oral administration of extracts or implantation of the device in the animal is observed for toxicity.  There are four categories: acute (24 hours), subacute (14 to 28 days) subchronic (90 days or 10% of an animals life span), and chronic (anything longer).This is outlined in ISO 10993-11.

Sub-acute/sub-chronic toxicity ISO 10993

Subacute and Subchronic Toxicity determines the systemic effect of repeated doses of materials or their extracts for no less than 24 hours and no greater than 10% of the total life span of the test animal. The test substance or extract is administered to the animal for 14 days, and is observed each day for signs of toxicity: weight change, appetite, signs of disease or abnormal behavior.  Then, the effects are evaluated and a histopathology is conducted on all animals.  This is outlined in ISO 10993-11.

Implantation with Histopathology ISO 10993

Implantation determines the local pathological effects on living tissue surrounding the implanted device.  A sample is implanted directly into the animal, appropriate for use of the device and is evaluated at the gross level and the microscopic level.  This is the equivalent to subchronic toxicity for materials. This is outlined in ISO 10993-6.