Blood air partition coefficient

Results in Table 31.3 indicate that the combination of TS and TC descriptors resulted in a highly predictive RR model = 0.895) the addition of three-dimensional and QC indices to the set of independent variables did not result in significant improvement in model quality. It may be noted that we have observed such results for various other physicochemical and biological properties including mutagenicity [25,54], boiling point [55], blood air partition coefficient [37], tissue air partition coefficient [46], etc. [24,30,45,56]. Only in limited cases, e.g., halocarbon toxicity [12], the addition of QC indices after TS and TC parameters resulted in significant improvement in QSAR model quality. 

Basak, S. C., Mills, D., El-Masri, H. A., Mumtaz, M. M., Hawkins, D. M. Predicting blood air partition coefficients using theoretical molecular descriptors. Environ. Toxicol. Pharmacol. 2004, 16, 45-55. 

Used to derive acute inhalation Minimal Risk Level (MRL) of 0.05 ppm (50 ppb) animal dose extrapolated to human dose according to method of EPA (1989d) values of blood/air partition coefficients assumed to be equal for animals and humans dose adjusted for 1 ess-than-continuous exposure (8 hours/24 hours), and divided by an uncertainty factor of 100 (10 for extrapolation from animals to humans, and 10 for human variability). 

Chloroform absorption depends on the concentration in inhaled air, the duration of exposure, the blood/air partition coefficient, the solubility in various tissues, and the state of physical activity which influences the ventilation rate and cardiac output. Pulmonary absorption of chloroform is also influenced by total body weight and total fat content, with uptake and storage in adipose tissue increasing with excess body weight and obesity. 

Pulmonary absorption of volatile anesthetics across the alveolar-capillary barrier is very rapid because of the relatively high lipid-water partition coefficients and small molecular radii of such agents. The driving force for diffusion is a combination of the blood-air partition coefficient (which is a measure of the capacity of blood to dissolve drug) and the difference in partial pressure between the alveoli and the arterial and venous blood. Agents with high blood-air partition coefficients require more drug to be dissolved in the blood for equilibrium to be reached. 

The blood levels of 1,1,1-trichloroethane in human subjects were lower following exposure to 350 ppm [1910 mg/m ] (approximately 2 mg/L) (Nolan et al., 1984) than those found in rats and mice following exposure to 150 ppm [820 mg/m ] (9.6 mg/L and 12.6 mg/L, respectively) (Schumann et al., 1982b). The species differences between humans and rats are probably the result of a lower 1,1,1-trichloroethane blood air partition coefficient and greater adipose tissue volume in humans (Dallas et al., 1989). 

Two groups of three male volunteers were exposed by inhalation to chlorodifluoromethane at either 327 or 1833 mg/m for 4 h. The average maximal blood concentrations were 0.25 and 1.36 (.ig/mL, respectively, and were achieved within 1 h of the beginning of exposure. The average blood/air partition coefficients for chlorodifluoromethane towards the end of the exposure period were 0.82 and 0.76, respectively, and the fat/air partition coefficients were 7.7 and 8.1. Thus, the fat/blood partition coefficient was estimated to be... 

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. 

Poulin, P., Krishnan, K. (1996a). A mechanistic algorithm for predicting blood air partition coefficients of organic chemicals with the consideration of reversible binding in hemoglobin. Toxicol. Appl. Pharmacol. 136 131-7. 

No studies were located in humans or animals regarding the absorption of inhaled 1,1-dichloroethane. However, its use as a gaseous anesthetic agent in humans provides evidence of its absorption. Furthermore, the volatile and lipophilic nature of 1,1-dichloroethane favors pulmonary absorption. Structurally related chlorinated aliphatics and gaseous anesthetics are known to be rapidly and extensively absorbed from the lung. The total amount absorbed from the lungs will be directly proportional to the concentration in inspired air, the duration of exposure, the blood/air partition coefficient of 1,1-dichloroethane, its solubility in tissues, and the individual s ventilation rate and cardiac output. One of the most important factors controlling pulmonary absorption is the blood/air partition coefficient of the chemical. The concentration of the chemical and the duration of exposure are also important determinants of the extent of systemic absorption. 

It is known that an isomer of 1,1 -dichloroethane, 1,2-dichloroethane, is well-absorbed following inhalation exposure. However, the blood/air partition coefficient for 1,2-dichloroethane is approximately four times that of 1,1-dichloroethane. This suggests that 1,1-dichloroethane would not be absorbed into the blood from air as readily as 1,2-dichloroethane, but it will still be well absorbed from the lung (Sato and Nakajima 1987). However, the excretion of metabolites in the urine indicated that 1,1-dichloroethane was absorbed following inhalation exposure, though the rate or extent of dichloroethane absorption is not known, since this represents theoretical estimates rather than actual data (Sato and Nakajima 1987). 

Comparative Toxicokinetics. The toxicokinetic pattern of 1,1,1-trichloroethane is qualitatively similar in humans, rats, and mice. There are major quantitative differences, however, including a higher blood air partition coefficient, higher respiratory and circulatory rates, and increased rate of metabolism in mice. This comparison has led to a suggestion that rats may be a better model for... 

Basak, S.C., Mills, D., Hawkins, D.M. and El-Masri, H.A. (2003a) Prediction of human blood air partition coefficient, a comparison of structure-based and property-based methods. Risk Anal., 23, 1173-1184. 

Hattis et al. (1993) reviewed a number of experimental studies of humans exposed to tetrachloroethylene and calculated ratios of arm blood to alveolar air tetrachloroethylene concentrations following inhalation exposure. These ratios suggest that the blood/air partition coefficient should be 15-18. Among the human blood/air partition coefficients estimated by in vitro methods (Table 2-4), the in vivo values are closest to the human blood/air partition coefficient of 19.8 estimated by Byczkowski and Fisher (1994) using the smear method. 

Metabolic parameters and blood air partition coefficients were also found to have the greatest impact on the prediction of the amount of tetrachloroethylene metabolized in PBPK models developed by Reitz et al. (1996). The models, developed for rats, mice, and humans, used values of 0.325,0.355, and 41.5 mg/hours for the three species, respectively, and Iv values of 5.62, 3.69, and 4.66 mg/L, respectively. Validation of the models showed a close correspondence to the rat data, but difficulties in fitting mouse data were attributed to difficulties in estimating the K. The model for humans was able to predict the distribution of tetrachloroethylene in blood and expired air, but metabolism data adequate to fully validate the model were not identified. 

The absorption, distribution, storage, and excretion of tetrachloroethylene are largely determined by its lipophilic nature. The blood/air partition coefficient estimated for humans is 10-20, the fat/air partition coefficient is 1,450-1,638, and the fat/blood partition coefficient is 125-159 (Byczkowski and Fisher 1994 Gearhart et al. 1993 Ward et al. 1988). Therefore, tetrachloroethylene is readily taken up by blood and is then distributed to fatty tissues where it is retained with a half-life of about 55 hours. The affinity of tetrachloroethylene for fat also results in its translocation into milk (Byczkowski and Fisher 1994). 

Whereas the rate of transfer of a solvent vapor between alveolar air and capillary blood is determined by its diffusivity, the equilibrium between these matrices is determined by the blood/air partition coefficient (X). This is the ratio of the concentration of the vapor in blood and air at 37 C, at equilibrium. Partition coefficients are commonly determined in vitro, and occasionally in vivo. Although considered constant at a particular temperature, partition coefficients may be affected by the composition of the blood. The blood/air partition coeffi-... 

The greater the blood/air partition coefficient, the eloser the arterial coneenlration will be to the venous concentration. 

Six healthy males were exposed to 72 and 144 ppm, as well as 142 ppm with 2 half hours of 100 W of exercise. Uptake of PERC was calculated from the minute volume and the concentration of PERC in breath. PERC was measured in breath and blood and TCA was measured in blood and urine. During the first hour of exposure the uptake was higher by 25% than during the last hour and retention decreased with time and with exercise. The mean ratio of the concentration of PERC in venous blood and the concentration of PERC in mixed exhaled air was 23. Assuming a mix-exhaled air to end-exhaled air ratio of 0.71, they estimated a blood/ air partition coefficient of 16. After 20 hours fi om the end of exposure the half-life was estimated to be 12-16 hours, after 50 hours the half-life was estimated to be 30-40 hours and after 100 hours it was estimated at approximately 55 hours. The authors estimated that 80-100% of PERC was excreted unchanged through the lung, and about 2% was excreted as TCA in the urine. 

Blood/air partition coefficient Breathing frequency Conductive zone of lungs... 

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