Toxicokinetics in Biomaterial and Device Safety Evaluation
Among the cardinal principles of toxicology is that the means by which an agent comes into contact with or enters the body (i.e., the route of exposure or administration) does much to determine the nature and magnitude of its effects (Goldstein et al., 1974; Jollow et al., 1982; Wartak, 1983; Pratt and Taylor, 1990). Accordingly, an understanding of the nature of device/tissue contact and the implications for absorption is essential. The fundamental safety factor is the ratio between what levels in the plasma (or at the target organ tissue) cause adverse effects to those levels which are present in the use of the device. For medical devices, it is rare that concentrations beyond the surface of the device are enough to cause systemic effects. In addition to the low concentrations overall, there is the complication that levels released from the device within the rst 24 hours of body contact are much higher than will ever be achieved subsequently (see Chapter 19 for further discussion on this point).