Integrated Biomaterials Science

Biocompatibility and Biological Tests 803
(James et al., 1997), but in 1992 FDA alerted the users about the possible
carcinogenicity of such materials and important manufacturers were forced
to discontinue production.
Hindsight tells us now that those further tests would have been
necessary in order to put safer prostheses on the market.
27.3.4. Reproductive Toxicity
The reproductive toxicity tests are described in the same standard of
carcinogenicity and mutagenicity, being different aspects of the same adverse
response to a material (ISO/EN 30993-3, 1993). These tests are indicated for
intrauterine devices, energy-depositing devices, and resorbable or leachable
materials or devices. Recently, some in vitro tests were designed to detect the
potential toxicity of a material or device during the reproductive cycle of the
cells. New experiments use transgenic animals, namely animals with their
cellular genetic patrimony changed by the DNA manipulation, for example,
by introducing human DNA segments.
In the future more importance is likely to be given to the in vitro tests
with cells containing manipulated DNA and the significance of the results
will increase due to the DNA manipulation and hence a closer affinity with
human DNA.
27.3.5. Irritation and Sensitization
These tests try to estimate the potential for contact sensitization of
materials or extracts (ISO/EN 30993-10, 1993). Amounts of leachables can
induce allergic or irritative reaction. A classic example is the allergic reaction
to nickel-containing metal alloys in contact with the skin, in women wearing
non-noble jewels.
These tests are also performed via a patch test. Guinea pigs are treated
with a patch embedded with an extract of the material and an untreated
patch as a control. Skin irritation zones are checked after stated times. The
sensitization test is divided into two phases: induction and challenge. The
results compare zones of the dorsal skin of guinea pigs treated with the
material extracts and a proven allergic compound (Freund compound).
27.3.6. Local Effect after Implantation
A series of implantation tests is described in order to assess the local
effect of the implantation of the material or its extracts in living tissue, from
macroscopic and microscopic points of view. Since the test is designed to
assess the biological interface developed by the material or device, it is not