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Table 21.2 Summary of Toxicity Tests and Related End Points I Chemical and physical properties For the chemical in question, probable contaminants from synthesis as well as intermediates and waste products from the synthetic process II Exposure and environmental fate A. Degradation studies hydrolysis, photodegradation, etc. B. Degradation in soil, water, under various conditions C. Mobility and dissipation in soil, water, and air D. Accumulation in plants, aquatic animals, wild terrestrial animals, food plants, and animals, etc. III In vivo tests A. Acute 1. LD50 and LC50 oral, dermal or inhaled 2. Eye irritation 3. Dermal irritation 4. Dermal sensitization B. Subchronic 1. 30- to 90-day feeding 2. 30- to 90-day dermal or inhalation exposure C. Chronic/reproduction 1. Chronic feeding (including oncogenicity tests) 2. Teratogenicity 3. Reproduction (multi-generation) D. Special tests 1. Neurotoxicity 2. Potentiation 3. Metabolism 4. Pharmacodynamics 5. Behavior IV In vitro tests A. Mutagenicity prokaryote (Ames test) B. Mutagenicity eukaryote (Drosophila, mouse, etc.) C. Chromosome aberration (Drosophila, sister chromatid exchange, etc.) V Effects on wildlife Selected species of wild mammals, birds, sh, and invertebrates: acute toxicity, accumulation, and reproduction in laboratory-simulated eld conditions

Furthermore, when the difference process xt at ct is driven by a stationary and ergodic point process fTn ; I < n < Ig, that is, x t x Tn ; then the uid queue process evolves as Qt QTn t Tn xTn ; t P Tn ; Tn 1 ; 10:11 t P Tn ; Tn 1 ;

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23 Miller, D M; Zhang, Y; Rahill, B M; Waldman, W J; Sedmak, D D Human cytomegalovirus inhibits IFN-a-stimulated antiviral and immunoregulatory responses by blocking multiple levels of IFN-a signal transduction J Immunol 1999, 162, 6107 6113 24 Weihua, X; Ramanujam, S; Lindner, D J; Kudaravalli, R D; Freund, R; et al The polyoma virus T antigen interferes with interferon-inducible gene expression Proc Natl Acad Sci USA 1998, 95, 1085 1090 25 Didcock, L; Young, D F; Goodbourn, S; Randall, R E The V protein of simian virus 5 inhibits interferon signalling by targeting STAT1 for proteasome-mediated degradation J Virol 1999, 73, 9928 9933 26 Didcock, L; Young, D F; Goodbourn, S; Randall, R E Sendai virus and simian virus 5 block activation of interferon-responsive genes J Virol 1999, 73, 3125 3133 27.

where q max q; 0 . From the recursion above, it is clear that the process Qt is essentially the same as the G=G=1 workload process. Hence, by the fundamental stability theorem of Loynes there exists a unique stationary solution to Eq. (10.11). We assume that fQt ; I < t < Ig is that stationary solution. 10.4.1 Fluid Queue with a Single On=Off Process

21.2 21.2.1

This section presents a complete asymptotic analysis of a uid queue with a single subexponential on=off arrival process. A general storage model in a two-state random environment was investigated by Kella and Whitt [39]. More formally, consider two independent sequences of i.i.d. random variables off def ftoff ; n ! 0g, fton ; n ! 0g, toff ton 0. De ne a point process Tn n n 0 0 Pn off on i 0 ti ti ; n ! 0; this process will be interpreted as representing the beginnings of off periods in an on=off process. Furthermore, de ne an on=off process at , with rate r, as at r if

Yokosawa, N; Kubota, T; Fujii, N Poor induction of interferon-induced 20 ,50 oligoadenylate synthetase (2-5 AS) in cells persistently infected with mumps virus is caused by decrease of STAT1-a Arch Virol 1998, 143, 1985 1992 28 Young, D F; Didcock, L; Goodbourn, S; Randall, R E Paramyxoviridae use distinct virus-speci c mechanisms to circumvent the interferon response Virology 2000, 269, 383 390 29 Leonard, G T; Sen, G C Effects of adenovirus E1A protein on interferon-signaling Virology 1996, 224, 25 33..

Regardless of the chemical tested and whether the test is for acute or chronic toxicity, all in vivo testing requires the reproducible administration of a known dose of the chemical under test, applied in a reproducible manner, that is generally related to the expected route of humans exposure. The nature and degree of the toxic effect can be

off Tn ton n off t < Tn ;

membranes and bronchial constriction. This irritation in turn increases the sensitivity of the airway to other airborne toxicants.

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