In vivo tests

The OECD, US-EPA, and EU have adopted in vivo test guidelines for the performance of toxicokinetic studies. The various guidelines are shown in Table 4.1 and are described further in the text below. 

The relevant test guideline for toxicokinetics in general is OECD TG 417 from 1984. This guideline is undergoing revision under the lead of the United States (OECD 2005). 

Toxicological Risk Assessments of Chemicals A Practical Guide 

Test Guidelines Adopted for Toxicokinetic Studies Title 

The relevant test guideline is Annex B.36 Toxicokinetics from 1988, which is similar to the OECD TG417. 

Traditionally the basis for the determination of toxicity has been administration of the test compound, in vivo, to one or more species of experimental animal, followed by examination for clinical signs of toxicity and/or mortality in acute tests. In addition pathological examination for tissue abnormalities is also performed, especially in tests of longer duration. The results of these tests are then used by a variety of extrapolation 

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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). 

Disinfection tests can be classified according to the test organism, ie, whether the test employs certain species of bacteria, fungi, or vimses classified as to whether it is a static test or a cidal test, as in a bactericidal vs bacteriostatic test or sporicidal vs sporistatic test or classified as to whether it is a microbial reduction test or an end-point test where all the organisms in the test are apparently killed. Procedures may be distinguished by in vitro or in vivo testing. Another way to consider tests is whether they are screening tests, practical type laboratory tests, or field tests. 

In all antiseptic testing, it is recognized that skin and mucous membranes to which products ate appHed cannot be disinfected or sterilized but it is possible to significantly reduce the population of transient and resident pathogenic bacterial flora. AH in vivo test methods requite a deterrnination of the bacteria on the skin before and after treatment. Because of the normal variation in bacterial population of the skin of different people, a number of people must be tested in order to make a statistical analysis of the results. Different parts of the body are used for different tests. In aH of the tests the details of the protocol ate extremely important and must be strictly adhered to in order to obtain reproducible results. 

Careful metabolic work on this drug by a group of French workers showed that the agent was in fact cleaved to sulfanilamide (83) and the amine, 84, in vivo. Testing of the two fragments revealed that the activity of the drug resided entirely in the sulfanilamide fragment. That compound in fact showed full activity when administered alone in vitro or in vivo. ... 

An in-vivo test in rodents (chromosomal damage in haematopoietic cells)... 

The vast majority of in vivo tests show no geno-toxicity of mono- and dialkyltins. Results from in vitro tests are variable, with little indication of DNA reactivity. There are, however, indications of clastogenicity and effects on spindle formation in mitosis in vitro. 

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). 

Iversen (1991) stresses the need for some in vivo testing for neurotoxicity and emphasizes the value of sensitive behavioral tests. Behavioral tests are described for mice and rats, which provide measures of mood, posture, CNS excitation, motor coordination, sedation, exploration, responsiveness, learning, and memory function. Such assays can function as primary screens for neurotoxicity before adopting a stepwise scheme of in vitro tests to discover more about the initial site of action of neurotoxic compounds. It is argued that the requirement for animal testing can be drastically reduced by adopting structured in vitro protocols such as these. 

Katsiadaki, I., Morris, S., and Squires, C. et al. (2006). Use of the three-spined stickleback (Gasterosteus aculeatus) as a sensitive in vivo test for detection of environmental antiandrogens. Environmental Health Perspectives 114, 115-121. 

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. 

The repressOT protein recognized only free acids inducers. However, as already observed, the in vivo tests can be realized with the corresponding esters, since they are hydrolysed in situ by esterases. 

Keller, J. C., Hammond, B. D., Kowlay, K. K. Brauer, G. M. (1988). Biological evaluation of zinc hexyl vanillate cement using two in vivo test methods. Dental Materials, 4, 341-50. 

Cowan, A. Simple in vivo tests that differentiate prototype agonists at opiate receptors. Iife Sci 28 1559-1570, 1981. 

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