Physiologically based models inhalation

No PBPK models specific for asbestos were located. While a number of physiologically-based models for deposition and clearance of inhaled insoluble material have been developed (ICRP 1994 Phalen et al. 

Jonsson, E., and Johanson, G. (2002). Physiologically based modeling of the inhalation kinetics of styrene in humans using a bayesian population approach. Toxicol Appl Pharmacol 179, 35 9. 

Note This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

Reddy MB, Dobrev ID, Plotzke KP, Andersen ME, Reitz RH, Morrow P, Utell M (2003) A physiologically based pharma-cokinetic model for inhalation of octamethylcyclotetrasiloxane (D4) in Human during rest and exercise. Toxicol Sci 72 3-18... 

Auton TR, Woollen BH A physiologically based mathematical model for the human inhalation pharmacokinetics of 1,1,2-trichloro-l,2,2-trifluoroethane. Int Arch Occup Environ Health 63 133-138, 1991... 

Paustenbach DJ, Clewell HJ, Gargas ML, et al. 1988. A physiologically based pharmacokinetic model for inhaled carbon tetrachloride. Toxicol AppI Pharmacol 96 191-211. 

Physiological toxicokinetic models have been presented describing the behaviour of inhaled butadiene in the human body. Partition coefficients for tissue air and tissue blood, respectively, had been measured directly using human tissue samples or were calculated based on theoretical considerations. Parameters of butadiene metabolism were obtained from in-vitro studies in human liver and lung cell constituents and by extrapolation of parameters from experiments with rats and mice in vivo (see above). In these models, metabolism of butadiene is assumed to follow Michaelis-Menten kinetics. 

Tardif et al. (1992, 1993 a, 1997) have developed a physiologically based toxicokinetic model for toluene in rats (and humans—see Section 4.1.1). They determined the conditions under which interaction between toluene and xylene(s) occurred during inhalation exposure, leading to increased blood concentrations of these solvents, and decreased levels of the hippurates in urine. Similar metabolic interactions have been observed for toluene and benzene in rats (Purcell et al., 1990) toluene inhibited benzene metabolism more effectively than the reverse. Tardif et al. (1997) also studied the exposure of rats (and humans) to mixtures of toluene, we/a-xylene and ethylbenzene, using their physiologically based pharmacokinetic model the mutual inhibition constants for their metabolism were used for simulation of the human situation. 

Nihlen, A., and G. Johanson. 1999. Physiologically based toxicokinetic modeling of inhaled ethyl tertiary-butyl ether in humans. Toxicol. Sci. 51 (2) 184-194. 

A physiologically based pharmacokinetics (PBPK) model based on the ventilation rate, cardiac output, tissue blood flow rates, and volumes as well as measured tissue/air and blood/air partition coefficients has been developed (Medinsky et al. 1989a Travis et al. 1990). Experimentally determined data and model simulations indicated that during and after 6 hours of inhalation exposure to benzene, mice metabolized benzene more efficiently than rats (Medinsky et al. 1989a). After oral exposure, mice and rats appeared to metabolize benzene similarly up to oral doses of 50 mg/kg, above which rats metabolized more benzene than did mice on a per kg body weight basis (Medinsky et al. 1989b). This model may be able to predict the human response based on animal data. Benzene metabolism followed Michaelis-Menton kinetics in vivo primarily in the liver, and to a lesser extent in the bone marrow. Additional information on PBPK modeling is presented in Section 2.3.5. 

Frank, R. 1980. S02-particulate interactions recent observations. Am. J. Ind. Med. l(3-4) 427-434. Frederick, C.B., M.L. Bush, L.G. Lomax, K.A. Black, L. Finch, J.S. Kimbell, K.T. Morgan, R.P. Subramaniam, J.B. Morris, and J.S. Ultman. 1998. Apphcation of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways. Toxicol. Appl. Pharmacol. 152 (1) 211-231. 

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