Interspecies comparisons

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. 

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. 

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. 

Taya A, Carmack DB, Muggenburg BA, et al. 1992. An interspecies comparison of the phagocytosis and dissolution of 241Am02 particles by rat, dog and monkey alveolar macrophages in vitro. Int J Radiat Biol 62(l) 89-95. 

It is assumed the equivalent human doses can be scaled on the basis of relative surface area, although metabolic differences may be important in interspecies comparison. 

FIGURE 17.5. The use of in vitro techniques in performing interspecies comparisons. 1, correlation of in vitro with in vivo observations 2, development of parallel in vitro systems in man 3, comparison of in vivo sensitivity of different species 4, potential toxicity in vivo 5, comparison of in vivo sensitivity of different species. 

The steady-state liver concentrations of chlordecone were similar in male and female rats and mice at each of the doses. These levels may, therefore, be important for interspecies comparisons since chlordecone is not metabolized in rats but is metabolized in humans. 

Daston GP, Rogers JM, Versteeg DJ, et al. 1991. Interspecies comparisons of A/D ratios A/D ratios are not constant across species. Fundam Appl Toxicol 17 696-722. 

R. C. Scott, M. A. Corrigan, F. Smith, and H. Mason. The influence of skin structure on permeability An intersite and interspecies comparison with hydrophilic penetrants. J. Invest. Dermatol. 96 921-925 (1991). 

L. Grislain, M. T. Mocquard, J. F. Dabe, M. Bertrand, W. Luijten, B. Marchand, G. Res-plandy, M. Devissaguet, Interspecies Comparison of the Metabolic Pathways of Perin-dopril, a New Angiotensin-Converting Enzyme (ACE) Inhibitor , Xenobiotica 1990, 20, 787 - 800. 

If sufficient data are available, substance-specific PBPK models should always be given preference over the use of general scaling factors. However, PBPK models were considered not to replace all of the sub-factors in the interspecies comparison and should, by definition, only include toxicokinetic differences. A further extrapolation factor for toxicodynamic differences between the species needs to be discussed. 

A second extrapolation step for toxicokinetic and toxicodynamic variability was recommended if interspecies comparisons involve, with a certain statistical probability, the occurrence of an above-average sensitivity in humans as compared with the test animal species. 

Voisin, E.M., M. Ruthsatz, J.M. Collins, and P.C. Hoyle. 1990. Extrapolation of animal toxicity to humans Interspecies comparisons in drug development. Regul. Toxicol. Pharmacol. 12 107-116. 

Daniel FB, Schut HAJ, Sandwisch DW, et al Interspecies comparisons of benzo[ ]pyrene metabolism and DNA-adduct formation in cultmed human and animal bladder and tracheobronchial tissues. Cancer Res MAI 2M 4729, 1983... 

Mechanisms involved in chlorine dioxide- and chlorite-induced oxidative stress, such as methemoglobinemia in humans and animals, would be expected to be similar across species. However, the database of pharmacokinetic and health effects information for chlorine dioxide or chlorite does not include studies in which interspecies comparisons were made. 

Pentsuk N, van der Laan JW (2009) An interspecies comparison of placental antibody transfer new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol 86 328-344... 

Submission documents should contain an interspecies comparison including details of the exposure at which any effects were found and a discussion of the relationship to the clinical exposure. Interspecies comparison can be used to help determine whether an effect in animals is relevant for clinical treatment in humans. 

Vogel, E. and Natarajan, A.T. The relation between reaction kinetics and mutagenic action of monofunctional alkylating agents in higher eukaryotic systems Interspecies comparisons. IN deSerres, F.J. and Hollaender, A., eds. Chemical Mutagens Principles and Methods for Their Detection, Volume 7. New York Plenum Press. 1982. p. 295-336. 

Hepatic peroxisome proliferation has not been evaluated in studies of human subjects or systems treated with di(2-ethylhexyl) adipate. However, interspecies comparisons with other peroxisome proliferators, along with the role of PPARa in this response, indicate that humans can reasonably be predicted to be refractory to induction of peroxisome proliferation and hepatocellular proliferation by di(2-ethylhexyl) adipate. 

Lewis JL, Rhoades CE, Bice DE, et al. 1992. Interspecies comparison of cellular localization of the cyanide metabolizing enzyme rhodanese within olfactory mucosa. Anat Rec 232(4) 620-627. 

Kharasch ED et al Compound A uptake and metabolism to mercapturic acids and 3,3,3-trifluoro-2-fluoromethoxypropanoic acid during low-flow sevoflurane anesthesia Biomarkers for exposure, risk assessment, and interspecies comparison. Anesthesiology 1999 91 1267. [PMID 10551576]... 

Graves, R.J., Coutts, C. Green, T. (1995) Methylene chloride induced DNA damage an interspecies comparison. Carcinogenesis, 16, 1919-1926... 

Jenness, R. 1982. Interspecies comparison of milk proteins. In Developments in Dairy Chemistry, Vol. I Proteins. P.F. Fox (Editor). Applied Science Publishers, New York. 

Lippmann, M., and Schlesinger, R. B. Interspecies comparisons of particle deposition and mucociliary clearance in tracheobronchial airways. J. Toxicol. Environ. Health 13(2-3) 441-469, 1984. 

An inverse correlation of sleep duration with longevity (r = -0.52) was found across 53 mammalian species, albeit these data are open to several interpretations (19). This interspecies comparison supports the hypothesis that long sleep may have an adverse causal effect on mortality, or conversely, that long wake may be life-preserving. 

Integrated summary of data from all studies and analysis of pertinent findings for interstudy and interspecies comparisons. Narrative summary for each study report describing the notable features and results of each study. A comprehensive study for notable findings in related studies for each species and notable species differences should be provided. 

Crouch, E., and R. Wilson. Interspecies comparison of carcinogenic potency. J. Toxicol. Environ. Health 5 1095-1118, 1979. 

The QSAR was developed for chemicals considered to act by a single mechanism of toxic action, non-polar narcosis, as defined by Verhaar et al. (1992), and therefore has a clear mechanistic basis. Non-polar narcosis has been established experimentally by using the Fish Acute Toxicity Syndrome methodology (McKim et al., 1987). The QSAR is based on a descriptor for hydropho-bicity (log Kow), which is relevant to the mechanism of action (i.e., toxicity results from the accumulation of molecules in biological membranes). There are numerous regression models based on log Kow for this mechanism of action, so the development of such models has enabled interspecies comparisons (Dimitrov et al., 2003). 

Woo, S., Jusko, W. J. Interspecies comparison of pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (rH-EPO). Drug Metabolism and Disposition 2007 (in press). 

Ahner, B.A., Kong, S., and Morel, F. (1995) Phytochelatin production in marine algae. 1. An interspecies comparison. Limnol. Oceanogr. 40, 649-657. 

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