A simple approach to validation of directed‐flow nose‐only inhalation chambers

Abstract

Directed-flow nose-only exposure systems are designed and operated so that the genuine test atmosphere is dynamically delivered to each exposure port and exhaled air from exposed animals is immediately exhausted without the possibility of other animals rebreathing this atmosphere. This technique is particularly useful for preventing uncontrolled changes of exposure atmospheres, stimulating breathing activity due to the rebreathing of exhaled carbon dioxide, and the conserving a test material that is available only in limited quantities. The intricate relationship of the delivered flow of air at each exposure port relative to the respiratory minute volume of the exposed animal appears to be critical for the state-of-the-art performance of directed-flow nose-only exposure systems. This analysis revealed that the determination of carbon dioxide concentrations at different inhalation chamber locations, including exposure ports, is a simple and cost-effective procedure to evaluate whether the rebreathing of atmospheres can be excluded. It has been shown that directed-flow systems need to be operated at an exposure air flow rate greater than 2.5 times the respiratory minute volume of the exposed animal or optimally approximately 0.75 l min(-1) per rat exposure port ( approximately 3.75 times the minute volume of young adult rats) to prevent higher CO(2)-concentrations occurring.

Retrospective analysis of 4-week inhalation studies in rats with focus on fate and pulmonary toxicity of two nanosized aluminum oxyhydroxides (boehmite) and pigment-grade iron oxide (magnetite): The key metric of dose is particle mass and not particle surface area

“…Simulations were based using a respiratory minute volume of 1 l/min/kg-rat. This respiratory minute volume has been determined under conditions similar to this study (Pauluhn and Thiel, 2007). During exposure days, a fraction of the dose increment was added to each of the arrays, and the total accumulated lung dose was then calculated by the equation shown above over Fig.…”

Attempts to counteract phosgene-induced acute lung injury by instant high-dose aerosol exposure to hexamethylenetetramine, cysteine or glutathione

“…For dose calculations a respiratory minute volume of 1 L × min −1 × kg −1 was used. This respiratory minute volume was determined under nose-only exposure conditions using volume displacement plethysmographs (Pauluhn and Thiel, 2007). Similar values have been reported by Mauderly (1989).…”

“…Technical details of the validation and use of this inhalation chamber system have been published previously (Pauluhn, 2006a;Pauluhn and Thiel, 2007;Pauluhn, 2010). In brief, a controlled flow of phosgene were discharged from the cylinder into a continuous flows of conditioned dry air and then entrained into the plenum of a nose-only inhalation chamber (inhalation chamber dimensions: inner diameter = 14 cm, outer diameter = 35 cm (two-chamber system), height = 25 cm (internal volume = about 3.8 L).…”

“…The fractions of drug deposited within the entire respiratory tract and in the pulmonary region was estimated by MPPD2 software (Anjilvel and Asgharian, 1995;RIVM, 2002) using the particle size data from cascade impactor analyses (Table 1). Of note is that a directed-flow nose-only exposure system was used for exposure which minimizes the rebreathing of atmosphere (Pauluhn and Thiel, 2007). For the calculation of the total inhaled dose a "deposition efficiency" of 1 was used whereas the alveolar dose was calculated based on the "P" fraction as shown in Figure 2.…”

Comparative assessment of the sensory irritation potency in mice and rats nose-only exposed to ammonia in dry and humidified atmospheres

“…Inhalation exposure system. Under dynamic conditions the various concentrations of gas atmospheres were attained by metering pure ammonia gas from a cylinder into a conditioning system from which it was entrained into the intake of the directed-flow nose-only inhalation chamber (Pauluhn and Thiel, 2007). A Telab BF 411 pump (TELAB Laboratory Dosing Pumps, Solingen, Germany) was used as gas metering device.…”