In vitro and Other Short-Term Tests

Tests for immunotoxicity are not required by all regulatory agencies, but it is an area of great interest, both in the fundamental mechanisms of immune function and in the design of tests to measure impairment of immune function. Both of these aspects are discussed in detail in Chapter 19. 

6 IN VITRO AND OTHER SHORT-TERM TESTS 21.6.1 Introduction 

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Metabolizing systems for in vitro short-term tests are most frequently derived from rat liver, but other species deserve consideration. Significant differences exist in the hepatic metabolism of various rodent species. For example, guinea pig liver does not activate A -2-fluorenylacetamide. Aflatoxin Bi and... 

Silk fibers or monolayers of silk proteins have a number of potential biomedical applications. Biocompatibility tests have been carried out with scaffolds of fibers or solubilized silk proteins from the silkworm Bombyx mori (for review see Ref. [38]). Some biocompatibility problems have been reported, but this was probably due to contamination with residual sericin. More recent studies with well-defined silkworm silk fibers and films suggest that the core fibroin fibers show in vivo and in vivo biocompatibility that is comparable to other biomaterials, such as polyactic acid and collagen. Altmann et al. [39] showed that a silk-fiber matrix obtained from properly processed natural silkworm fibers is a suitable material for the attachment, expansion and differentiation of adult human progenitor bone marrow stromal cells. Also, the direct inflammatory potential of silkworm silk was studied using an in vitro system [40]. The authors claimed that their silk fibers were mostly immunologically inert in short and long term culture with murine macrophage cells. 

Metabolism and pharmacokinetic studies have greater relevance when conducted in both sexes of young adult animals of the same species and strain used for other toxicity tests with the test substance. The number of animals used in metabolism and pharmacokinetic studies would be sufficient to reliably estimate population variability. This usually means a separate (but parallel) set of groups of animals in rodent studies. A single set of intravenous and oral dosing results from adult animals, when combined with some in vitro kinetic results, may provide an adequate data set for the design and interpretation of short-term, subchronic and chronic toxicity studies. 

Immunosuppression can cause a reduction of the animal s resistance to infection and, under certain conditions, also to an increased susceptibility to tumorigenesis (tumor-promotion). In contrast, hyperactivity of the immune system can result in autoimmune diseases or increase the sensitivity to allergies. While it is difficult to identify the mechanisms of the effect(s) of immuno-toxicity it is relatively easy to detect such properties. Information can be provided by investigating special parameters from the rat used in short-term or sub chronic rodent studies (type I tests) (FDA/FDCA 1993). The other category of tests uses in vitro techniques (type II tests). 

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