Mass median aerodynamic diameter MMAD

FIGURE 5.28 Estimated overall airway deposition as a function of initial particle size and particle hygroscopicity for particles with mass median aerodynamic diameters (MMAD) between 0.1 and 10 p.m. ° Geometric dispersion, a measure of particle size distribution, principally affects only smaller MMAD,... 

The various pharmacopeias outline appropriate methods for aerodynamic assessment of partiele size distribution. The USP defines the size distribution through mass median aerodynamic diameter (MMAD) and geometrie standard deviation (GSD). 

Both from deposition studies and force balances it can be derived that the optimum (aerodynamic) particle size lies between 0.5 and 7.5 pm. Within this approximate range many different subranges have been presented as most favourable, e.g. 0.1 to 5 pm [24], 0.5 to 8.0 pm [25], 2 to 7 pm [26] and 1-5 pm [27-29]. Particles of 7.5 pm and larger mainly deposit in the oropharynx [30] whereas most particles smaller than 0.5 pm are exhaled again [31]. All inhalation systems for drug delivery to the respiratory tract produce polydisperse aerosols which can be characterized by their mass median aerodynamic diameter (MMAD) and geometric standard deviation (oq). The MMAD is the particle diameter at 50% of the cumulative mass curve. 

Used to derive a chronic inhalation Minimal Risk Level (MRL) of 2 x 10" mg/m nickel for soluble nickel salts dose adjusted for intermittent exposure (6/24 hours, 5/7 days), multiplied by the Regional Deposited Dose Ratio (0.9714 for pulmonary region deposition mass median aerodynamic diameter [MMAD] = 2.5 pm, sigma = 2.4 pm), and divided by an uncertainty factor of 30 (3 for extrapolation from animals to humans, and 10 for human variability). 

The half-life of nickel in the lungs of rats exposed by inhalation has been reported to be 32 hours for nickel sulfate (mass median aerodynamic diameter [MMAD] 0.6 pm) (Hirano et al. 1994b), 4.6 days for nickel subsulfide ( Ni3S2 activity, median aerodynamic diameter [AMAD] 1.3 pm), and 120 days for green nickel oxide ( NiO, AMAD 1.3 pm) (Benson et al. 1994). Elimination half-times from the lung of rats of 7.7, 11.5, and 21 months were calculated for green nickel oxide with MMADs of 0.6, 1.2, and 4.0 pm, respectively (Tanaka et al. 1985, 1988). 

The Mass Median Aerodynamic Diameter (MMAD) was reported as a lower limit of 0.8 pm and an upper limit of 1.2 pm for an average of 1.0 pm (pg 33 Hartman 1990). The Geometric Standard Deviation (GSD) was reported as a lower limit of 1.2 pm and an upper limit of 1.5 pm for an average of 1.35 or 1.4 pm. The Regional Deposited Dose Ratio (RDDR) from Table HI under the ER (Extrarespiratory effects) column is... 

Minimal data are available from typical inhalation studies in laboratory animals to allow evaluation of extent or dose-dependency in inhaled arsenic absorption. Beck, Slayton and Farr (2002) reported a study in which rabbits were exposed to 0.05, 0.1, 0.22, or 1.1 mg m-3 of arsenic trioxide 8 hours/day, seven days/week for eight weeks. The particle size (mass median aerodynamic diameter, MMAD) ranged from 3.2 to 4.1pm. On the basis of minimal elevation of inorganic arsenic in plasma until exposure levels were at or above 0.22 mg m-3, the authors concluded that systemic uptake of arsenic trioxide following inhalation exposure was low and did not contribute significantly to body burden until relatively high levels of exposure were achieved. 

The mass median aerodynamic diameter (MMAD) is defined as the aerodynamic diameter which divides the aerosol mass size distribution in half. 

We routinely use nose-only inhalation exposure of B(a)P aerosol to evaluate the consequence of prenatal exposure to this toxicant on physiological and behavioral endpoints. The properties of this B(a)P aerosol are shown in Figure 17.4. The aerosol typically exhibits a trimodal distribution with a 93% cumulative mass less than 5.85 pm, 89% cumulative mass less than 10 pm, 55.3% cumulative mass less than 2.5 pm, and 38% less than 1 pm. Fifty-five percent of the aerosol generally has a cumulative mass less than PM2.5 and the mass median aerodynamic diameter (MMAD) + geometric standard deviation for this mode is consistently 1.7 =E 0.085 pm. For several years we employed a rat model exposing timed pregnant dams to inhalation concentrations of 25, 75, and 100 pg/m. ... 

Thus, Eqs. (2) and (3) enable us to convert the volume-equivalent particle size distribution into aerodynamic-equivalent distribution for any flow regime. The characteristic mean diameters are dy (volume geometric) and (volume aerodynamic). Although dp is numerically close to the mass-median aerodynamic diameter (MMAD) often used for the aerosols, it is better defined for asymmetrical distribution, so often observed for respiratory powders. 

Metal Oxide Dust Zinc oxide metal fumes generated at 550°C aggregated into chains of ultrafine primary particles, whose secondary particles had a mass median aerodynamic diameter (MMAD) of 0.3 p,m (300 nm) (10). Fumes would contain both fine accumulation particles (100 to 600 nm) and ultrafine particles (3, 11). 

Measurements of the quantity and quality of the aerosolized drug allow characterizing the dosing properties of inhalation devices in vitro. Multistage im-pactors are used to assess particle mass and mass distribntion of an aerosol, and methods are available to estimate the mass median aerodynamic diameter (MMAD) of the aerosol as well as the dose of delivered from and retained within an inhalation system. 

The addition of (NH4)2C03 and magnesium stearate (MgST) to the formulation improved the aerodynamic properties of the Trojan particles and resulted in a mass median aerodynamic diameter (MMAD) of 2.2 0.81m. 

C) For contaminants consisting primarily of particles with mass median aerodynamic diameters (MMAD) of at least micrometers, an air-purifying respirator equipped with any filter certified for particulates by NIOSH. 

The median diameter corresponds with the 50 % value of a cumulative number, volume or mass percent distribution as function of the diameter. Fifty percent of the volume (number or mass) of the aerosol is in larger, and 50 % is in smaller particles than the median diameter. For a volume distribution it is the volume median diameter, for a mass distribution the mass median diameter. When the mass percent is expressed as a function of the aerod3mamic diameter, reference can be made to the mass median aerodynamic diameter (MMAD). 

Winkler et al. (1998) reported that the activity size distribution of Pb in ambient aerosols was unimodal (log-normal) and associated with submicron aerosols of about 0.5 to 0.6 pm. On average, the activity median aerodynamic diameter, AMAD, of Pb-aerosols (0.53 pm) has been found to be significantly lower than the average mass median aerodynamic diameter, MMAD (0.675 pm), and higher than or at most equal to the respective surface median aerodynamic diameter, SMAD, (0.465 pm) of the aerosols SMAD < AMAD < MMAD. Variation of the atmospheric processes resulted in a variability of the activity median aerodynamic diameter, AMAD, between 0.28 and 0.74 pm for Pb. While in the winter period (October to April) the AMAD of Pb averaged 0.595 pm, in the summer period Pb was associated with significantly smaller aerosols (AMAD 0.43 pm). 

The activity median aerodynamic diameters (AMADs) of Pb (Table 2.3) and mass median aerodynamic diameters (MMADs) of SO (Table 2.4) determined from a series of low- pressure (LPI) cascade impactor measurements made during the period January to October (1985) by Papastefanou and Bondietti (1987) are illustrated in Figure 2.7. The Pb data were derived from measurements made at the same time as and from measurements made to compare Pb versus Pb. The mean aerodynamic diameter of Pb was about three times smaller than that of SO ". Much less sulfate was found in the aerosol fraction below 0.08 pm... 

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