Biomedical Engineering Reference
In-Depth Information
Table 2
Skin reaction scoring scheme
Irritation
score
Reaction
Erythema and eschar formation
No erythema
0
Very slight erythema (barely perceptible)
1
Well-defined erythema
2
Moderate erythema
3
Severe erythema (beet-redness) to eschar formation
preventing grading of erythema
4
Edema formation
No edema
0
Very slight edema (barely perceptible)
1
Well-defined edema (edges of area well defined by
definite raising)
2
Moderate edema (raised approximately 1 mm)
3
Severe edema (raised more than 1 mm and extending
beyond exposure area)
4
determine if leachables or soluble chemicals are present that would
cause some degree of toxicity.
The design for the acute toxicity tests used for medical devices
can vary, but they are most often based on the United States
Pharmacopeia (USP) systemic toxicity test [
18
]. In this method,
device extracts are dosed by the intravenous and intraperitoneal
routes. The USP method was originally designed for pharmaceuti-
cal containers, i.e., drug vials. Since the vehicle or drug product
vehicle for pharmaceuticals can vary, a set of four vehicles is used in
this method: (1) saline, (2) 5% alcohol in saline, (3) vegetable oil,
and (4) polyethylene glycol (PEG). For ISO 10993-11 testing [
8
],
saline and vegetable oil extracts are considered sufficient for this
screening assay. In this test method, mice are used and dosed
intravenously (saline-based materials) or intraperitoneally (non-
saline solution). Mice are observed for clinical symptoms of toxicity
such as lethargy, hyperactivity, convulsions, weight loss, and death.
Animals are observed for a minimum of 3 days. For extracts a
relatively large dose volume, 50 ml/kg of body weight, is used.
While this dose volume is large, it is tolerated by mice. Since the
quantity of leachables is generally expected to be low, this high dose
volume improves the sensitivity of the assay. However, this high
dose volume can present issues when extracting devices that are
soluble. When testing a soluble medical device, a physiologically
