Inhalation exposure to jp‐8 jet fuel alters pulmonary function and substance p levels in fischer 344 rats

Abstract

In a simulated military flightline exposure protocol, Fischer 344 rats (F344) were used to investigate the pulmonary effects of JP-8 jet fuel inhalation. Exposures were nose only and for 1 h daily. Groups were exposed for 7 days (7D) or 28 days (28D). Each exposure group had a matched longitudinal control group (LC7 and LC28). Exposure concentrations of 520 mg m-3 caused an increase in dynamic compliance after 7 days of exposure, but compliance changes were not seen with continued exposure (28D, 495 mg m-3). Pulmonary resistance was increased in both 7- and 28-day JP-8-exposed groups. Changes in pulmonary function were accompanied by a decrease in substance P concentrations from the bronchoalveolar lavage fluid (BALF). No significant change was observed in BALF levels of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, which is a marker of endothelial cell function. The JP-8-exposed rats gained significantly less weight during the study period than the LC7 and LC28 groups, and the lungs of the 7D group were heavier by wet lung/body weight ratio (WtL/WtB). Alveolar clearance of technetium-labelled diethylenetriamine pentaacetate ([99mTc]DTPA) was increased in jet fuel-exposed groups. Light microscopy showed no pathological evidence of lung injury. Recovery from the early pulmonary effects of JP-8 inhalation occurred with continued exposure, as seen by recovery of pulmonary compliance and WtL/WtB.

Distillates (petroleum), hydrotreated light [MAK Value Documentation, 2016]

“…Examination of the lungs with a light microscope did not reveal any adverse findings. A NOAEC was not obtained (Pfaff et al 1995).…”

Correlation Between In Vivo and In Vitro Pulmonary Responses to Jet Propulsion Fuel-8 Using Precision-Cut Lung Slices and a Dynamic Organ Culture System

“…Morphological evaluation after acute JP-8 aerosol exposures showed lesions following a range of doses up to 113 mg/m 3 (4,17,19). Subsequent in vitro experiments in our labs explored the role of epithelial barrier function upon JP-8 exposure.…”

“…Initial in vivo experiments in our labs revealed that aerosol exposure results in the targeting of distal airways as shown by enhanced respiratory permeability to 99m TcDTPA (4,17,18). Morphological evaluation after acute JP-8 aerosol exposures showed lesions following a range of doses up to 113 mg/m 3 (4,17,19).…”

A Reevaluation of the Threshold Exposure Level of Inhaled Jp-8 in Mice

“…Past studies have linked JP-8 exposure to a multitude of adverse health effects including developmental, hepatic, immunological, neurological, pulmonary, and dermal effects (Cooper and Mattie, 1996;Dossing et al, 1985;Harris et al, 1997;Smith et al, 1997;Pfaff et al, 1995;Ullrich, 1999). However, perhaps of greatest importance are the effects of JP-8 jet fuel on the respiratory system and consequently, pulmonary function.…”

“…On a physiological level, several studies have demonstrated deleterious effects on pulmonary function including increased pulmonary resistance and increased respiratory permeability (Robledo and Witten, 1998). On a cellular level, pathological changes including interstitial edema, injured alveolar septa, damaged bronchiolar epithelium and alveolar type II cells, and epithelial necrosis have also been observed, indicating significant cellular damage as a result of JP-8 exposure Pfaff et al, 1995;Robledo and Witten, 1998;Robledo et al, 2000). On a biochemical level, altered expression of certain chemical mediators has also been observed, including macrophage inflammatory protein-2 (MIP-2), tumor necrosis factor-alpha (TNF-α), and anti-inflammatory mediator prostaglandin E 2 (PGE 2 ) (Wang et al, 2001).…”