Biomedical Engineering Reference
In-Depth Information
Table 9.14
Pyrogen test procedures required by ISO 10993 guidelines
ISO 10993-11
Number of animals:
Three rabbits required; comparison of febrile response in test animals to
baseline temperature for evaluation of pyrogenicity potential
Test duration:
Test measurement intervals: every 30 min for 3 h
Evaluation:
Cut-off for positive febrile response: 0.5°C
Table 9.15
ISO 10993-3 guidelines used historically for assessing the effects of
device or material implantation
ISO 10993-3
Time point(s) of assessment:
Suffi cient to achieve steady state (e.g. 2, 4, 6 and 12 weeks). Can be
signifi cantly longer due to expected duration of clinical implantation. Now
commonly modifi ed in design to also address concerns covered under
subchronic and chronic toxicity.
Number of animals:
At least three per time period of assessment
Number of samples of evaluation:
At least eight per time period for test and control
Evaluation criteria:
Comparative evaluation of responses to test and control materials
Implantation tests
: These tests evaluate the local toxic effects on living tis-
sue (at both the gross and microscopic levels), from a sample material that is
surgically implanted into an appropriate animal implantation site (e.g. mus-
cle, bone) for 7-90 days. The ISO procedure is outlined in Table 9.15 below.
Mutagenicity (genotoxicity)
: The application of mammalian or non-
mammalian cell culture techniques for the determination of gene mutations,
changes in chromosome structure and number, and other DNA or gene tox-
icities caused by test materials and/or extracts from materials. Selected tests
looking for gene mutations (Ames or mouse lymphoma) and chromosomal
aberrations (CHO, mouse micronucleous and sister chromatid exchange)
should generally be employed. ISO procedure is outlined in Table 9.16
below.
Subchronic toxicity
: The determination of harmful effects from multiple
exposures to test materials and/or extracts during a period of one day to less
than 10% of the total life of the test animal (e.g. up to 90 days in rats).
Chronic toxicity
: The determination of harmful effects from multiple
exposures to test materials and/or extracts during a period of 10% to the
