Inhalation, lung dose estimation

For estimating the lung dose after inhalation by means of models three parameters of air activity are necessary ... 

Exposure to natural sources of radiation is unavoidable. Externally, individuals receive cosmic rays, terrestrial X-rays, and gamma radiation. Internally, naturally occurring radionuclides of Pb, Po, Bi, Ra, Rn, K, C, H, U, and Th contribute to the natural radiation dose from inhalation and ingestion. Potassium-40 is the most abundant radionuclide in foods and in all tissues. The mean effective human dose equivalent from natural radiations is 2.4 milliSieverts (mSv). This value includes the lung dose from radon daughter products and is about 20% higher than a 1982 estimate that did not take lung dose into account (Table 32.4). 

Several popular empirical models adopted for respiratory pharmaceutical use owe their existence to the need for radiological dose estimation of inhaled particulates, beginning with the ICRP Task Group on Lung Dynamics [5], now superseded by ICRP [6] or alternatively NCRP [7], Yeh et al. [8] compare the ICRP [6] and NCRP [7] models, with the largest differences between these models occurring for particles that are smaller than those used in respiratory drug delivery (i.e, <0.1 pm diameters). Other empirical models include Yu et al. [9] and Davies [10]. 

The dose of inhaled E25 was estimated from phamacokinetic studies in cynomol-gus monkeys. Monkeys were exposed to a single dose of aerosolized E25 for 20 minutes by head-only inhalation using a Pari-IS2 nebulizer. Total volume inhaled during the aerosol exposure was measured and the concentration of E25 in the inhaled air was determined by filter sampling. Aerosol droplet size was also measured by cascade impaction. The estimated deposited dose in the lungs from these determinations was 117 p.g. To evaluate the kinetics of E25 deposited on the lung surface, samples of the ELF were taken by BAL and the total E25 concentration measured by ELISA. Samples of BAL were taken at 0, 1, 2, 4, 8, 12, and 24 hours postinhalation. Only two BAL samples were taken from a single animal. Two animals were used for each time point. Urea concentrations in BAL fluid were used for dilution corrections to estimate ELF (23). 

Altshuler, B., M. Nelson, and M. Kushner, Estimation of lung tissue dose from the inhalation of radon and daughters, Hlth. Phys. 10 1137-1164 (1964). 

The effect of concentration on the fate of [14C] -hexane after inhalation exposure has been studied in Fischer 344 rats (Bus et al. 1982). The disposition of radioactivity was dose-dependent, with 12, 24, 38, and 62% of the acquired body burden excreted as -hexane by the lung with increasing exposure concentration (500, 1,000, 3,000, and 10,000 ppm, respectively). In contrast, 38, 31, 27, and 18% of the body burden of radioactivity was recovered as expired C02 and 35, 40, 31, and 18% was recovered in the urine with increasing -hexane concentration (expired air and urine were collected for 72 hours after exposure). Radioactivity remaining in the tissues and carcass 72 hours after exposure represented 6.1, 8.8, 7.4, and 5.4% of the body burden for the respective exposures. The dose-dependent elimination of radioactivity was apparently due in part to an inhibition of -hexane metabolism reflected by a decrease in total 14C02 and urinary 14C excretion after 10,000 ppm exposure compared to the 3,000 ppm exposure. Half-lives for excretion were estimated from the data. Urinary half-time for excretion of radioactivity was 12.7 hours at 500 ppm. 

Inhaled (volatile) anesthetics are delivered to the lungs in gas mixtures in which concentrations and flow rates are easy to measure and control. However, dose-response characteristics of volatile anesthetics are difficult to quantify. Although achievement of an anesthetic state depends on the concentration of the anesthetic in the brain (ie, at the effect site), concentrations in the brain tissue are obviously impossible to measure under clinical conditions. Furthermore, neither the lower nor the upper ends of the graded dose-response curve defining the effect on the central nervous system can be ethically determined because at very low gas concentrations awareness of pain may occur. Moreover, at high concentrations there is a high risk of severe cardiovascular and respiratory depression. Nevertheless, a useful estimate of anesthetic potency can be obtained using quantal dose-response principles for both the inhaled and intravenous anesthetics. 

Zanamivir is delivered directly to the respiratory tract via inhalation. Ten to twenty percent of the active compound reaches the lungs, and the remainder is deposited in the oropharynx. The concentration of the drug in the respiratory tract is estimated to be more than 1000 times the 50% inhibitory concentration for neuraminidase, and the pulmonary half-life is 2.8 hours. Five to fifteen percent of the total dose (10 mg twice daily for 5 days for treatment and 10 mg once daily for prevention) is absorbed and excreted in the urine with minimal metabolism. Potential adverse effects include cough, bronchospasm (occasionally severe), reversible decrease in pulmonary function, and transient nasal and throat discomfort. 

Repeated Dose Exposure. Available studies on the effects of repeated inhalation exposure of animals to BCME (Leong et al. 1971, 1981) indicate that an exposure level of 0.1 ppm is a NOAEL for most systemic effects in rats, while 1.0 ppm leads to significant injury to lung in mice. Further studies to confirm these estimates and to determine both NOAEL and LOAEL values in each species would be useful in the protection of occupationally exposed workers. 

To calculate the dose to the lung from inhalation of insoluble particulate activity of long radioactive half-life, it is necessary to estimate the clearance from the P region. ICRP (1979) assumed a clearance half-life of 500 d. Booker et al. (1967) found half-lives in the range 150-300 d in subjects who had inhaled polystyrene particles labelled with 51Cr, but the radioactive half-life of this isotope (27 d) restricted the duration of the measurements to 100 d. In more recent... 

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