Inhalation Toxicology Methods: The Generation and Characterization of Exposure Atmospheres and Inhalational Exposures

Abstract

In this review, we outline the need for laboratory-based inhalation toxicology studies, the historical background on adverse health effects of airborne toxicants, and the benefits of advance planning for the building of analytic options into the study design to maximize the scientific gains to be derived from the investments in the study. We then discuss methods for: 1) the generation and characterization of exposure atmospheres for inhalation exposures in humans and laboratory animals; 2) their delivery and distribution into and within whole-body exposure chambers, head-only exposure chambers, face-masks, and mouthpieces or nasal catheters; 3) options for on-line functional assays during and between exposures; and 4) options for serial non-invasive assays of response. In doing so, we go beyond exposures to single agents and simple mixtures, and include methods for evaluating biological responses to complex environmental mixtures. We also emphasize that great care should be taken in the design and execution of such studies so that the scientific returns can be maximized both initially, and in follow-up utilization of archived samples of the exposure atmospheres, excreta, and tissues collected for histology.

Geometry optimization, factors screening, and introduce a predicting mathematical model of inhalation exposure chamber’s performance.

“…Therefore, the stability and uniformly distribution of the particle concentration in the target zone are ensured during the test duration. The uniform distribution of TM in the respiratory zone of the studied subjects is an important criterion for validating studies on the toxicology of suspended particles [7,16,4,2]. So far many inhalation exposure chambers have been designed and used, but in most cases, variations in the concentration of the TM have been observed in the target zones [2].…”

“…The heterogeneous distribution of TM in the exposure chamber results in temporal and spatial variations in TM concentration and can expose a group under study to heterogeneous concentrations, therefore in interpreting dose-response results, the overestimation or underestimation of toxicity of TM may be attributed to the target concentration [3]. The uniformity of TM distribution in exposure chambers depends on several factors such as chamber geometry, flow type, particle size, and particle density [2,[4][5][6], which should be taken into account in designing exposure chambers. Most existing exposure chambers are designed in such a way that by changing the conditions of the test, and material, as well as by changing the animal and its location, it is necessary to examine the possible variation in concentration in the respiratory zone of laboratory animals.…”

Vinyl Chloride and High-Fat Diet as a Model of Environment and Obesity Interaction

“…Indeed, data from this model recapitulated results observed in humans exposed to VC, such as the impact on metabolic pathways 20 , oxidative stress and mitochondrial dysfunction 4 . Other mouse models of inhalation, such as head-only and nose-only models 21 , require that the animal be restrained, causing stress to the animal. Here, this whole-body exposure method does not require injection or unneeded stress to the animals.…”

Development of a large-scale computer-controlled ozone inhalation exposure system for rodents

“…There are several reviews describing guidelines on the best practices for inhalation toxicology studies (Phalen 1976; Dorato 1990; Pauluhn 2003; Wong 2007; Chen and Lippmann 2015). Detailed manuscripts on the design of inhalation exposure systems for gases such as O 3 and various other classes of airborne toxicants such as particulate matter, aerosols, and vapors have also been published (O’Shaughnessy et al 2003; Wong 2007; McKinney and Frazer 2008; Goldsmith et al 2011).…”

“…Detailed manuscripts on the design of inhalation exposure systems for gases such as O 3 and various other classes of airborne toxicants such as particulate matter, aerosols, and vapors have also been published (O’Shaughnessy et al 2003; Wong 2007; McKinney and Frazer 2008; Goldsmith et al 2011). Our goal was to design and implement an ozone exposure system that complies with published guidelines (Phalen 1976; Chen and Lippmann 2015; OECD 2018), while at the same time meeting our specific experimental requirements. General design considerations for whole-body inhalation toxicology studies include a delivery system for clean air, compatible/inert construction materials, control and characterization of the exposure atmosphere, and maintenance of suitable environmental conditions without the buildup of waste gases (Phalen 1976).…”