Citation:

Vance, S., Y. Kim, J. Dye, W. Williams, Mette C. Schladweiler, Ian Gilmour, I. Jaspers, AND S. Gavett. The Impacts of Inhaled Burn Pit-Related Smoke and Intratracheally Instilled Smoke Extracts on Breathing and Pulmonary Toxicity in Mice. Society of Toxicology, San Diego, California, March 27 - 31, 2022.

Impact/Purpose:

The purpose of this project is to characterize health effects of inhaled smoke from burning of some key building materials found in military burn pits (e.g. plywood, cardboard, and plastics) under controlled combustion conditions, and relate these effects to key chemical constituents of the smoke. In this study we assessed acute health effects of these smoke emissions or particulate matter condensates in mice, with the goal of comparing the health impacts when administered by inhalation or by intratracheal instillation. Intratracheal dosing gave higher deposited PM than inhaled PM, but real-time measurements of respiratory function with inhaled smoke generally gave more significant effects than instilled PM, indicating real-time measurements are more sensitive for elucidating respiratory effects of smoke constituents.

Description:

Exposure to particulate matter (PM) and gaseous components of smoke from combustion of synthetic materials such as plastic (PL), plywood (PW) or cardboard (CB) found in military burn pits is associated with reduced respiratory function and increased pulmonary inflammation. We previously found that respiratory function decrements in mice exposed to burn pit smoke constituents is a sensitive marker of toxicity. Here we compared the relative sensitivity of real-time plethysmography (RTP) in nose-only exposed mice compared with whole body plethysmography (WBP) in mice exposed previously by intratracheal instillation (IT). Mice were exposed nose-only to whole or PM-filtered smoke from military burn pit-related constituents (PL, PW, or CB at 40 mg PM/m3 generated under smoldering (510 °C) combustion conditions for 1 hour on 2 consecutive days while undergoing RTP), or they were instilled with 100 mg of PM condensates and assessed by WBP 2-4 hours after instillation. During RTP inhalation exposure, whole CB smoke reduced breathing frequency (f) an average of 126 breaths/min (bpm) from baseline which was unaffected by HEPA filtration, suggesting a mostly gaseous component of toxicity. In contrast to inhalation, IT exposure to CB PM reduced f by 89 bpm suggesting that CB PM at this dose (IT ~3-fold > inhaled) also had significant pulmonary effects. Inhalation of PL was associated with the greatest decrement in f (-167 bpm), whereas IT exposure to PL did not significantly affect breathing parameters, suggesting that the gaseous components were responsible for this decrease. Similar effects of PL were found with respect to minute volume (MV); inhalation of PL reduced MV by 16 mL while IT PL did not change MV. In contrast, PW and CB had significant reductions for both inhalation and IT; CB reduced MV by 10 mL during inhalation and reduced MV by 19 mL post-IT. Bronchoalveolar lavage neutrophils were significantly increased following IT exposure to PW, whereas no inflammation was observed following inhalation exposure, likely due to the lower total deposited dose. These results show that while IT exposures allow for precise dosing and comparative toxicity measurements, RTP is a more sensitive model for elucidating respiratory effects. (This abstract does not represent U.S. EPA policy; DoD award #W811XWH-18-1-0731 to I.J.)

Record Details: