Species and strains

Commercial PCBs Toxic and Biochemical Effects. PCBs and related halogenated aromatic hydrocarbons ehcit a diverse spectmm of toxic and biochemical responses in laboratory animals dependent on a number of factors including age, sex, species, and strain of the test animal and the dosing regimen (single or multiple) (27—32). In Bobwhite and Japanese quad, the LC q dose for several different commercial PCB preparations ranged from 600 to 30,000 ppm in the diet the LC q values for mink that were fed Aroclors 1242 and 1254 were 8.6 and 6.7 ppm in the diet, respectively (8,28,33). The... 

Another notable feature of the in vivo bacterial luminescence is seen in their emission spectra. Although the emission peak of in vitro bacterial luminescence is normally at about 490 nm, the in vivo emission peaks of various bacterial species and strains are significantly shifted from 490 nm, ranging from the shortest wavelength of 472 nm to over 500 nm. Some expanded notes concerning in vivo bacterial luminescence are given below. 

Energy transfer to fluorescent proteins. There are marked differences among the various bacterial species and strains in terms of the in vivo luminescence spectra. The emission maxima are spread mostly in a range from 472 to 505 nm (Seliger and Morton, 1968), but one of the strains, P. fischeri Y-l, shows a maximum at 545 nm (Ruby and Nealson, 1977), as shown in Fig. 2.3. However, the in vitro luminescence spectra measured with purified luciferases obtained from the various bacterial species and strains are all similar (Amax about 490 nm). The variation in the in vivo luminescence spectra may be due to the occurrence of an intermolecular energy transfer that increases the efficiency of light emission. 

The nitrogenase proteins are generally characterized by two letters indicating the species and strains of bacteria and the numerals 1 for the MoFe protein and 2 for the Fe protein. Thus, the Fe protein from Azotobacter vinelandii is Av2 and the MoFe protein from Klebsiella pneumoniae is Kpl. 

Animal studies have shown that tumors can result from both inhalation (Fukuda et al. 1983 Henschler et al. 1980 Maltoni et al. 1986) and oral exposure (Aima et al. 1994 Henschler et al. 1984 NCI 1976 NTP 1990) to trichloroethylene. Unfortunately, some of these studies (NCI 1976) are limited in that they use carcinogenic epoxide stabilizers with the trichloroethylene, which may contribute to the carcinogenicity. The studies also show different responses depending on the sex, species, and strains of animals used and do not point to a particular target organ for increased tumor incidence. Other studies are flawed because of excess... 

Stages in hazard characterization according to the European Commission s Scientific Steering Committee are (1) establishment of the dose-response relationship for each critical effect (2) identification of the most sensitive species and strain (3) characterization of the mode of action and mechanisms of critical effects (including the possible roles of active metabolites) (4) high to low dose (exposure) extrapolation and interspecies extrapolation and (5) evaluation of factors that can influence severity and duration of adverse health effects. 

Timmins, E. M. Howell, S. A. Alsberg, B. K. Noble, W. C. Goodacre, R. Rapid differentiation of closely related Candida species and strains by pyrolysis mass spectrometry and Fourier transform infrared spectroscopy. /. Clin. Microbiol. 1998,36, 367-374. 

Bowles, J. and McManus, D.P. (1993a) Rapid discrimination of Echinococcus species and strains using a polymerase chain reaction-based RFLP method. Molecular and Biochemical Parasitology 57, 231-240. 

Preliminary studies with 1,2-dimethylhydrazine were also reported 2/10, 5/10, and 5/5, rats died respectively, after a single 4-h exposure at 285, 338, or 435 ppm (Jacobson et al. 1955). During the exposure, the rats were restless and exhibited dyspnea, convulsions, and exophthalmos. Although an LC50 was not estimated, review of these data suggest that 1,2-dimethylhydrazine is somewhat less toxic under these experimental conditions in this species and strain. For 1,2-dimethylhydrazine, lethality was assessed over a 7-d period. 

Pyrethroid-induced neurobehavioral effects including clinical signs are known to be highly influenced by methodological changes in route, vehicle, dosing volume, species, and strain [19, 20]. The influence of the dose volume on the neurobehavioral effects after single oral administration was evaluated with... 

Jones, E. M., and Surewicz, W. K. (2005). Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids. Cell 121, 63-72. 

Jones, E. M., and Surewicz, W. K. (2005). Fibril conformation as the basis of species- and strain-dependent seeding specificity of mammalian prion amyloids. Cell 121, 63-72. Kad, N. M., Myers, S. L., Smith, D. P., Smith, D. A., Radford, S. E., and Thomson, N. H. (2003). Hierarchical assembly of beta2-microglobulin amyloid in vitro revealed by atomic force microscopy./. Mol. Biol. 330, 785-797. 

The choice of species and strain to be used in a carcinogenicity study is based on various criteria including susceptibility to tumor induction, incidence of spontaneous tumors, survival, existence of an adequate historical data base, and availability. 

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. 

An issue of obvious importance in test species selection is the degree to which test results can be reliably applied to human beings. As we noted in the last chapter this is one of the principal problems in the evaluation of human risk, and we shall get back to it in the later chapters on risk assessment. For now, emphasis is on the selection of animal species and strains for their known reliability as experimental subjects. To put it in stark (but honest) terms - the animals are used as toxicity measuring devices. 

In this section, a number of tumor types and mechanisms/mode(s) of action, which are believed to be of limited relevance for humans, are addressed. It must be stressed that it is important that each individual case must be thoroughly evaluated, and to take into consideration that the response of various laboratory species and strains may vary greatly and may change considerably over time. 

It is recommended that testing be performed in the most relevant species, and that laboratory species and strains which are commonly used in prenatal developmental toxicity testing be employed. The preferred rodent species is the rat and the preferred nonrodent species is the rabbit. Justification should be provided if another species is used (4). 

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