Other In Vivo Tests

Alternative in vivo challenge tests have been proposed, such as the nasal (Eyre and Nally 1971), and conjunctival tests, where local anaesthetics are applied locally to those mucous membranes. The subcutaneous injection of a test dose has been advocated by Incaudo et al. (1978). We cannot see any of these tests as being either convincingly reliable or less risky than the conventional skin tests. The single case of fatal reaction to the instillation of one drop of a local anaesthetic into the con- 

---

In case this hypothesis will be confirmed for a larger number of chemical compounds, this in-vitro system could be considered as a good candidate for the replacement of the Draize test because of its high sensitivity, objectivity, automatization degree and ethical acceptance. This test only reflect the inflammatory alterations of the Draize EIT and must therefore completed by other in vivo tests. 

A particular mode of neurotoxicity was discovered for tricresyl phosphate that correlated with the presence of the o-cresyl isomer (or certain other specific aLkylphenyl isomers) in the triaryl phosphates. Many details of the chemistry and biochemistry of the toxic process have been elucidated (139,140,143—146). The use of low ortho-content cresols has become the accepted practice in industrial production of tricresyl phosphate. Standard in vivo tests, usually conducted with chickens sensitive to this mode of toxicity, have been developed for premarket testing of new or modified triaryl phosphates. As of 1992, the EPA called for extensive new toxicity and environmental data on this group of products (147). The Vederal e ster AoQ xm. ci. calling for this... 

For many years it was beUeved that iodine, or some other halogen, had to be present to endow these compounds with thyromimetic activity. This was shown to be incorrect when a halogen-free analogue, DIMIT (3), was found to have 20% of the potency of T in a variety of in vivo tests (12). 

Since in vivo tests in exposed human populations would involve concomitant exposure to other toxicants, it would be difficult to assess the genotoxic potential of methyl parathion alone. Therefore, additional well-designed in vitro studies using human cell lines are needed to determine the effects of methyl parathion on various genotoxic parameters (e.g., sister chromatid exchange, chromosomal aberrations, unscheduled DNA synthesis). 

The term "bioenertness" is a relative one since few if any synthetic polymers are totally biocompatible with living tissues. The terra is used here on the basis of preUminary in vitro and in vivo tests, together with chemical evaluations based on analogies with other well-tested systems. Two different types of polyphosphazenes are of interest as bioinert materials those with strongly hydrophobic surface characteristics and those with hydrophilic surfaces. These will be considered in turn. 

Subcutaneous in vivo testing of these polymers (13,14) has shown minimal tissue response—similar, in fact, to the response to poly-(tetrafluoroethylene). These materials are candidates for use in heart valves, heart pumps, blood vessel prostheses, or as coating materials for pacemakers or other implantable devices. 

Other two sensors have been proposed and in this case, in vivo tests have been reported25 26, but none of the proposed pH sensors appears completely satisfactory. 

Toxicokinetic data can also be used to make informed decisions on testing of chemical substances. In specific circumstances, valid toxicokinetic data may be used to support a decision to omit testing for systemic effects, e.g., in cases where the toxicokinetic data provide sufficient evidence that a substance is not absorbed and therefore not systemically available, i.e., no plasma/blood concentrations were measurable and no parent compound or metabolites could be detected in urine, bile, or exhaled air. For example, in vivo testing for mutagenicity, reproductive toxicity, or carcinogenicity may be omitted if toxicokinetic data or other data indicate a lack of systemic availability. 

Information To Be Obtained from Other Studies Involving Repeated Exposure Although not aiming directly at investigating repeated dose toxicity per se, other available in vivo test guideline smdies involving repeated exposure of experimental animals may provide useful information on repeated dose toxicity. 

Since the 1970s, a number of reports on biomaterials other than SPU have also been presented, providing us with evidence which shows the important role played by microdomain structures in realizing excellent biomedical properties. For instance, an A-B-A type block copolymer (HEMA-St—HEMA) (See Sect. 4.2) was shown to form microdomain structure and to exhibit excellent blood compatibility in both in vitro and in vivo tests. 

There are now many different in vitro mutagenicity tests employing different strains of bacteria and also in vivo tests designed to detect mutations in higher organisms and mammalian systems. It is beyond the scope of this book to discuss these, but details can be found in other texts. 

Bivalirudin is a direct thrombin inhibitor that has found utility for reducing the rate of acute reocclusion in patients treated with PCI. It is preferential to heparin in PCI when HIT is present. This drug is a derivative of hirudin, which is a dedicated thrombin inhibitor with no other in vivo activities of significance. The molecule is semisynthetic the C-terminal of hirudin is linked by a polyglycine spacer to the tetrapeptide region of the N-terminal that reacts with the thrombin active site (22). It is monitored by the activated clotting time test. Its pharmacologic properties are shown in Table I. 

The vision literature contains a great variety of different absorption profiles for the chromophores of vision. They have been acquired using a variety of means. The chemist prefers to measure the absorbance of individual chromophores in a standard one centimeter cell as a function of wavelength. The chromophore is usually present in a dilute solution. The psychophysiologist prefers an in-vivo test under conditions of differential adaptation. The results from these two methods have shown considerable disparity. This work will show that, for the in-vivo situation (and adequate differential adaptation in the psychophysical situation), the actual L-channel peak is in human vision is at 625 nm. This is the peak wavelength observed in all other biological species. 

A detailed discussion of experimental in vitro and in vivo testing methodologies and results is not the purpose of this chapter. There are some comprehensive reviews covering this topic. For instance, the contribution by Oberdorster et al. [45] who have summarized recent data and highlighted gaps in this field two works [60, 61] review data on environmental and human effects of carbon nanotubes in relation to their properties a paper [62] that discusses toxicological endpoints of combustion-derived nanoparticles a review [63] of quantum dots toxicity an excellent review devoted to toxicity of particular nanomaterials classes by Borm et al. [26] and many others. 

Our purpose is to produce practical, chemically characterized and physically tested chemical sensors for in vivo applications in cardiology and, ultimately, other biomedical fields. The present main focus is on macro membrane-based pH sensors, reduction to micro size, in vivo testing and preliminary application by cardiologists. 

All other assays related to in vivo tests on allergens can only serve as a cognitive tool and assist the diagnostic process. The ultimate verification of allergenic properties of a diet or a dietary component should always be performed by an... 

---