Interspecies

Interspecies Between two different species, such as tomato and weeds. 

Patel BA, Boudinot FD, Schinazi RF, Gallo JM, Chu CK (1990) Comparative pharmacokinetics and interspecies scaling of 3 -azido-3 -deoxythymidine (AZT) in several mammalian species. J Pharmacobiodyn 13 206-211... 

Dedrick R, Bischoff KB, Zaharko DS. Interspecies correlation of plasma concentration history of methotrexate (NSC-740). Cancer Chemother Rep 1970 Apr 54(2) 95-101. 

Metabolic differences betw een humans and other animals may account for some of the interspecies differences in specific organ toxicity of trichloroethylene (see below). Among humans, sexual differences due mainly to the effects of body fat content on trichloroethylene absorption are expected based on PBPK modeling (see Section 2.3.5). 

The liver is an organ that shows variable effects from trichloroethylene among species, and this can probably be attributed to interspecies differences in metabolism (see Section 2.4.2.1). Specifically, the apparent difference in susceptibility to trichloroethylene-induced hepatocellular carcinoma between humans and rodents may be due to metabolic differences (see Section 2.4.2.3). Kidney effects are also variable among species. Humans and mice are less sensitive than rats. In rats exposed chronically to trichloroethylene, toxic nephrosis characterized as cytomegaly has been reported (NTP 1988). The kidney effects in rats do not seem to be related to an increase in alpha-2 -globulin (Goldsworthy et al. 1988). Effects on the nervous system appear to be widespread among species, presumably due to interactions between trichloroethylene and neuronal membranes. 

Comparative Toxicokinetics. In humans, the targets for trichloroethylene toxicity are the liver, kidney, cardiovascular system, and nervous system. Experimental animal studies support this conclusion, although the susceptibilities of some targets, such as the liver, appear to differ between rats and mice. The fact that these two species could exhibit such different effects allows us to question which species is an appropriate model for humans. A similar situation occurred in the cancer studies, where results in rats and mice had different outcomes. The critical issue appears to be differences in metabolism of trichloroethylene across species (Andersen et al. 1980 Buben and O Flaherty 1985 Filser and Bolt 1979 Prout et al. 1985 Stott et al. 1982). Further studies relating the metabolism of humans to those of rats and mice are needed to confirm the basis for differences in species and sex susceptibility to trichloroethylene s toxic effects and in estimating human heath effects from animal data. Development and validation of PBPK models is one approach to interspecies comparisons of data. 

We have developed a quantitative structure-activity model for the variations in potency among the nitrosamines and, more recently, a related model for the variation in target organ for a smaller set of nitrosamines. We are currently developing a model for interspecies variation in susceptibility toward carcinogenic nitrosamines. The model for organ selectivity requires terms for the parent nitrosamine as well as for the hypothesized metabolites while the model for potency variations contains terms only for the unmetabolized parent compound. 

All of the quantitative models are implicitly dose-dependent. This is of particular importance with respect to interspecies comparisons since it may be possible for the relative susceptibility of species to reverse on going from higher to lower doses. 

Interspecies Variations in Susceptibility. An Important assumption in the development of both the structure-potency model (eq, 1) and the structure-target-organ model (eq, 2) was that all of the test compounds were administered at equal daily... 

It does suggest, however, that our original assumptions concerning d were at least reasonable. In addition, the dose-depen-dent model can be manipulated to examine - in a general sense -some aspects of interspecies variations in susceptibility to nitrosamine carcinogenesis. 

With tso as an index of carcinogenicity, an interspecies relative potency (IRP) can be defined, e.g.,... 

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. 

McGowan C, R Fulthorpe, A Wright, JM Tiedje (1998) Evidence for interspecies gene transfer in the evolution of 2,4-dichlorophenoxyacetic acid degraders. Appl Environ Microbiol 64 4089-4092. 

The pathways and mechanism of interspecies transfer have been examined in syntrophic propionate-oxidizing organisms. 

Basu N, Stamler CJ, Loua KM, Chan HM. 2005a. An interspecies comparison of mercury inhibition on muscarinic acetylcholine receptor binding in the cerebral cortex and cerebellum. Toxicol Appl Pharmacol 205 71-76. 

A large degree of variation is apparent in retention rates for americium in the liver among various animal species (Durbin 1973), as indicated by measured or estimated liver clearance half-times of approximately 5-16 days in rats, 152 days in baboons, 1-10 years in dogs, and 10 years in Chinese hamsters. A liver clearance half-time of 2 years has been estimated for humans (Griffith et al. 1983). Refer to Section 3.5.1 for information regarding toxicokinetic mechanisms that may play a role in interspecies differences in liver retention of americium. 

Significant interspecies differences are apparent regarding liver retention rates of absorbed americium (Durbin 1973 Griffith et al. 1983) (see Sections 3.4.2.4 and 3.5.1 for more detailed information). 

However, no data were located to indicate significant interspecies differences in health effects associated with exposure to americium. 

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