Species extrapolation

If PBPK models for endosulfan exist, the overall results and individual models are discussed in this section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. 

The overall results and individual PBPK models for trichloroethylene are discussed in this section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. Several PBPK models have been developed for inhaled trichloroethylene. In an early model by Fernandez et al. (1977), the human body was divided into three major compartments or tissue groups the vessel-rich group (VRG), muscle group (MG), and adipose tissue (fat) group (FG). The distribution of trichloroethylene in these... 

True zwitterionic compounds are rare among drugs. The oral absorption of truly zwitterionic compounds is poor unless the compound is a substrate for an absorptive biological transporter as in an a-amino acid which is a substrate for the PepTl nutrient transporter. The aqueous solubility of a true zwitterionic compound will be at a minimum at the isoelectric point which unfortunately for many compounds happens close to the neutral pH at which oral absorphon occurs. Species extrapolation predicting oral absorphon and pk/pD from preclinical animal tests to man are difficult for zwitterions. 

Species extrapolation. Data in both animals and humans (children and adults) describing the absorption, distribution, metabolism, and excretion of lead provide the biological basis of the biokinetic model and parameter values used in the IEUBK Model. The model is calibrated to predict compartmental lead masses for human children ages 6 months to 7 years, and is not intended to be applied to other species or age groups. 

Sheppard, C.R.C. and D.J. Bellamy. 1974. Pollution of the Mediterranean around Naples. Mar. Pollut. Bull. 5 42-44. Shore, R.F. 1995. Predicting cadmium, lead and fluoride levels in small mammals from soil residues and by species-species extrapolation. Environ. Pollut. 88 333-340. 

Species extrapolation. No species extrapolation was attempted in this model. Results from in vitro studies in rat liver homogenates were used to estimate kinetic parameters for the catabolism of n-hcxane and synthesis of 2,5-hexanedione. 

Species extrapolation. No species extrapolation was attempted in this model. 

Species extrapolation. Extrapolation of this model from the rodent studies on which it is based to human exposure has not yet been done. 

Species Extrapolation. The Corley model used species-specific information to outline the model parameters little extrapolation of information among mice, rats and humans was required. Certain parameters previously reported in the scientific literature were assumed, however, such as body weight, percentage of body weight, and percentage of blood from the heart (i.e., percentage of cardiac output of... 

Species Extrapolation. The Reitz model used the same species and physiologic parameters that the Corley model utilized (average body weights, organ percentage of body weight, blood flow, etc.) for model predictions. See Table 2-4 for these parameters. However, the model assumed equivalent intrinsic sensitivity of mouse and human hepatocytes. 

Species Extrapolation. The human was the only species addressed by the McKone model. No extrapolation between species was addressed in this model. 

Comparative Toxicokinetics. Pharmacokinetics studies have not been performed under conditions analogous to those of the carcinogenicity studies. Therefore, it is not possible to determine systemic levels of the compound associated with the reported effects. Pharmacokinetics data developed under exposure conditions associated with biological effects would markedly increase the possibility of improved species extrapolation for evaluating the true potency of 3,3 -dichlorobenzidine. 

Emerging Molecular and Compntational Approaches for Cross-Species Extrapolations. Portland, Oregon, 18 to 22 Jul 2004. Published by SETAC and CRC Press, 2006. 

Comparative Toxicokinetics. No studies were located in which toxicokinetics of chlorine dioxide or chlorite were examined in humans. Chlorine dioxide is used as a drinking water disinfectant and readily forms chlorite (CIO2 ) in aqueous environments. Therefore, humans would be most likely to encounter chlorine dioxide or chlorite via the oral exposure route. Currently, available toxicokinetic information is restricted to animal studies. Additional studies could be designed to examine toxicokinetics in humans orally exposed to chlorine dioxide or chlorite. Results of human and animal studies could then provide a basis for development of PBPK models for species extrapolation. 

Beliveau, M., Lipscomb, J., Tardif, R. and Krishnan, K. (2005) Quantitative structure-property relationships for inter species extrapolation of the inhalation pharmacokinetics of organic chemicals. Chem. Res. Toxicol.,... 

Hengstler JG, Oesch F. Interspecies differences in xenobiotic metabolizing enzymes and their importance for inter species extrapolation of toxicity. In Ballantyne B, Marrs TC, Syversen T, eds. General and Applied Toxicology. Vol. 1. London Macmillan, 2000. 

The effect observed in the test system should occur at equivalent doses in the test system and in humans after adjustment for differences in metabolism, body weight, surface area, etc. (across-species extrapolation). 

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