Marsha E. O'Neill

A small whole-body exposure chamber for laboratory use

With the development of transgenic and specialized mouse strains, there is an increased need for inhalation exposure systems designed for smaller exposure groups. An inhalation exposure chamber, designed specifically for the exposure of up to 40 mice, was characterized. The chamber was fabricated from 0.32-cm-thick (1 / 8 -in) aluminum sheets with outside dimensions of 61 cm long by 32 cm high by 34 cm deep, resulting in an internal volume of 65 L. Two stainless-steel open-mesh cages, separated by an absorbent barrier, can be stacked within the central portion of the chamber. Access is provided through a gasketed door with a safety-glass face. Tests were performed to determine the chamber leakage rate, degree of mixing, and spatial variation of two aerosols within the chamber. Results indicated that the fractional leakage rate was 0.0003 min -1, well below a reported criterion for an operating chamber. Chamber operation gave similar mixing performance with, or without, use of an interior fan. For aerosols with a mass median aerodynamic diameter (MMAD) of 2.56 µm and 3.14 µm, the spatial variation of particulate matter concentration resulted in coefficients of variation (CVs) of 4.8% and 11.0%, respectively. These CV values are comparable to those obtained from similar studies involving other inhalation exposure chambers.

Biomonitoring for assessment of organic dust-induced lung inflammation

Inhalation exposure to particulate matter containing endotoxin (or lipopolysaccharide (LPS)) occurs in a variety of occupations. Nasal lavage and induced sputum have been used to evaluate lung inflammation resulting from such exposures. Whole blood assay (WBA) measures cytokine production of leukocytes after ex vivo stimulation with LPS. The present study examined the effectiveness of WBA for evaluating inflammatory responses and susceptibility. C3HeB/FEJ mice were tolerised by LPS injection or sham tolerised with saline. Animals then inhaled either swine barn dust extract containing endotoxin or saline. Bronchoalveolar lavage (BAL) fluid was assayed for leukocyte counts and pro-inflammatory cytokines (interleukin-6, tumour necrosis factor-α). Whole blood was stimulated with 10 or 100 ng·mL-1 of LPS, incubated for 5 or 18 h and assayed for cytokines. Barn dust-exposed groups revealed significantly higher total cells, neutrophils and cytokines in BAL compared with saline-exposed groups. Animals tolerised to LPS and exposed to barn dust demonstrated lower cellular and cytokine BAL responses. Similarly, WBA yielded significantly elevated cytokines with barn dust exposure and reduced responses with tolerisation. This study demonstrates the efficacy of whole blood assay as a biomarker of inhalation exposure to inflammatory agents and its use for assessing susceptibility to organic dust-induced lung inflammation.