Retention Patterns for Inhaled Particles in the Lung

Abstract

In the absence of adequate data exclusively from studies of inhaled particles in people, the results of inhalation studies using laboratory animals are necessary to estimate particle retention in exposed people. To make accurate projections from animal studies and the limited human data, it is necessary to consider species similarities and differences in lung retention and accumulation patterns for inhaled materials. This paper reviews species similarities and differences in pulmonary retention and clearance for inhaled particles, with emphasis on animal species most commonly used in inhalation toxicology research (rats, guinea pigs, dogs, and nonhuman primates). Simulation models for these four species and for humans were used to compare projected lung burdens which would be accumulated during chronic inhalation exposures. These simulation models project an eightfold difference among these species in the lung concentration of particles per gram of lung after a 2-y chronic inhalation exposure to the same aerosol for 8 h d-1, 5 d wk-1. The largest lung accumulation would occur in guinea pigs, the smallest in rats. To reach the same target lung concentration of particles in the lungs of both animals would therefore require about an eightfold difference in air concentration of the exposure material. These comparisons are useful for selecting appropriate laboratory animal species to study as surrogates for humans, for setting aerosol concentrations to use in inhalation studies, and for making approximations of lung burdens that would result from defined exposure scenarios.

Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System

“…Using the mouse inhaled ED 90 of 0.9 μg/kg for ipratropium, an allometric exponent of 0.67, a mouse body mass of 0.03 kg, and a human body mass of 60 kg; an estimated human ED 90 of 0.07 μg/kg ((0.9*(0.03/60) (1-0.67) = 0.07) can be calculated as the predicted human deposited dose from our mouse data. This predicted value is comparable to the actual human efficacious deposited dose of 0.26 μg/kg, which can be calculated from the delivered dose of 40 μg 39 divided by the human body mass of 60 kg multiplied by a human oral inhalation pulmonary deposition fraction 16 of 0.4 ((40/60)*0.4 = 0.26). An estimate of the effective human inhaled deposited dose also helps to plan the delivered doses used in inhalation toxicology studies required for clinical trials 40 .…”

“…Unlike humans, who can inhale a substantial dose of concentrated aerosol from an inhaler in a single deep breath, continuous generation of a respirable (0.5-5 μm mass median aerodynamic diameter, MMAD) aerosol, for up to an hour, is required to deposit an efficacious drug dose into a spontaneously breathing rodent's lungs in a nose-only inhalation system 16 . Aerosol generators (jet nebulizer or the Wright dust feed 17 ) that can continuously produce the required aerosol particle size and concentration for nose-only inhalation studies are not very efficient at generating high quality (respirable) aerosols.…”

Toxicity of particulate matter from incineration of nanowaste

“…45 For most nanomaterials, their mass fractions in PM were no more than 0.62% at any loading in the waste. 52,53 However, at this PM concentration, the fluorescence intensity of DCF, which should have increased, actually decreased, possibly because of the high surface area of PM that adsorbed the DCF and the enzyme. Thus, the subsequent discussion hinges on the fact that the amount of nanomaterials in samples subjected to ROS and toxicity assays was very low in most cases, but it is possible that they catalyzed formation or destruction of other toxic compounds in the PM.…”

Current intelligence bulletin 69: NIOSH practices in occupational risk assessment.

“…Particles that deposit in the pulmonary region are cleared primarily by alveolar macrophages that phagocytose (engulf) particles, where they are dissolved or transported to the TB region for mucociliary clearance [Schlesinger 1985]. Clearance of poorly soluble particles can differ across species because of differences in the rates of mucociliary transport in the conducting airways and macrophagemediated clearance from the alveolar region [Miller 2000;Snipes 1989]. Pulmonary clearance is approximately 10 times slower in humans than in rats, based on first-order clearance assumptions [Snipes 1989].…”

“…Clearance of poorly soluble particles can differ across species because of differences in the rates of mucociliary transport in the conducting airways and macrophagemediated clearance from the alveolar region [Miller 2000;Snipes 1989]. Pulmonary clearance is approximately 10 times slower in humans than in rats, based on first-order clearance assumptions [Snipes 1989].…”