Relevance of Animal Models

Although the usual animal model for i.t. studies is the rat [45, 47, 48, 54], studies on dogs [50, 54], rabbits [49] and guinea pigs [55] have also been reported. 

A detailed review of i.t. dosing has recently been published [46], which provides practical details of the technique. 

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Hofmann,W., and F. Daschil, The Relevance of Animal Models for Radionuclide Inhalation in Man, in Current Concepts in Lung Dosimetry, Proc. of the 30th Annual Meeting of the Radiation Research Society at Salt Lake City 1982 (D.R. Fisher, ed) pp 95-102, Utah... 

Bach, P. H., and T. L. Hardy. 1985. Relevance of animal models to analgesic-associated papillary necrosis in humans. Kidney International 28 605-613. 

Wester, R.C. and Noonan, RK. (1980). Relevance of animal models for percutaneous absorption, International Journal of Pharmaceutics, 7 99-110. 

Lyons TJ, Christu CN, Larsen FS (1975) Ammoniated mercury ointment and the nephrotic syndrome. Minn Med 58 383-384 Maibach H, Boisits E (eds) (1982) Neonatal skin structure and function. Marcel Dekker, New York Marshall JD, Schneider RP (1977) Systemic argyria secondary to topical silver nitrate. Arch Dermatol 113 1077-1079 Marzulli F, Maibach H (1975) Relevance of animal models the hexachlorophene story. In Maibach H (ed) Animal models in dermatology. Churchill Livingstone, Edinburgh, pp 156-167 Marzulli F, Maibach H (eds) (1996). Dermatoxicology, 5th edn. Hemisphere, Washington... 

Contrary to the Isofl, S-Eq possesses an asynunetric carbon in position C3. This gives it a three-dimensional shape closer to that of 17p-E2 (Fig- 77.2c, d). Thanks to this, 5-Eq exhibits a greater affinity for the ERs than its precursor Daid [72], and has a greater effect on bone resorption prevention [79]. This also raises the question of the relevancy of animal models when considering the putative effect of soy or a soy extract on human health. 

It may be that any peripherally adversive stimulus — especially one that stimulates sympathetic activity — thus has the potential to activate brain areas of prime importance in the formation of anxiety symptoms. As a result of pharmacological challenge studies, biochemical assays, neuroimaging and studies of animal models, a number of centrally acting neurotransmitters, and their relevant neural circuits, are implicated in anxiety. These neurotransmitters include norepinephrine, serotonin, GABA, neuropeptide Y, cholecystokin and substance P. 

UCL takes into account measurement uncertainty in the study used to estimate the dose-response relationship, such as the statistical uncertainty in the number of tumors at each administered dose, but it does not take into account other uncertainties, such as the relevance of animal data to humans. It is important to emphasize that UCL gives an indication of how well the model fits the data at the high doses where data are available, but it does not indicate how well the model reflects the true response at low doses. The reason for this is that the bounding procedure used is highly conservative. Use of UCL has become a routine practice in dose-response assessments for chemicals that cause stochastic effects even though a best estimate (MLE) also is available (Crump, 1996 Crump et al., 1976). Occasionally, EPA will use MLE of the dose-response relationship obtained from the model if human epidemiologic data, rather than animal data, are used to estimate risks at low doses. MLEs have been used nearly universally in estimating stochastic responses due to radiation exposure. 

Relevance of animal species and models used for preclinical studies. 

The use of nonrelevant animal species is discouraged as the results of such studies may be misleading (per ICH S6). Therefore the next option, when available, is to substitute a relevant transgenic animal model for a pharmacologically relevant species. Transgenic animal models for human EpCAM have been developed, but they either have a different tissue expression pattern from that seen in humans [41,43] or the model has not been validated [40], making them unsuitable for the evaluation of the safety of anti-EpCAM immunotherapeutics. 

Population characteristics -h Measured in humans -h Large population size possible -h Full range of sensitive subpopulations possible + Measured in humans - Limited number of subjects + Possible to study sensitive subpopulations - Extrapolation to humans + Large group size possible - Homogeneity of animal model population and environmental factors-relevance to human ... 

De Sesso, J. M. (1993). The relevance to humans of animal models for inhalation studies fo cancer in the nose and upper airways. Qual Assur 2, 213-231. 

In summary, high priority has to be given to the validation of the popliteal lymph node assay (or other local lymph node approaches) and to the further development of predictive animal assays using routes of exposure that are more directly relevant to the human experience. These advancements would significantly enhance the usefulness of animal models and testing strategies for autoimmunity and autoimmune diseases. 

Physiological and anatomical characteristics for different species are summarised in Table 7.7 (Dressman and Yamada 1991). Some additional information of relevance for the use of animal models in formulation studies can be found in other review articles (Kararli 1995 Ritschel 1987). 

Loisel S, Ohresser M, Pallardy M, Dayd e D, Berthou C, Cartron G, Watier H. Relevance, advantages and limitations of animal models used in the development of monoclonal antibodies for cancer treatment. Crit Rev Oncol Hematol 2007 62 34-42. 

A family of animal models that support the evaluation of nanomaterials. In order to obtain FDA approval, the animal models must be relevant to the human model. The animal models need to identify and verify nanomaterial fate, toxicity, pharmacokinetics, and immune response. 

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