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

Abstract

-C57BL/6 mice were nose-only exposed to JP-8 jet fuel at average concentrations of 45, 267, and 406 mg JP-8/m 3 for 1 hr/d for 7 days to further test the hypothesis that exposure to JP-8 concentrations below the current permissible exposure level (PEL) of 350 mg/m 3 will induce lung injury, and to validate a new "in-line, real-time" total hydrocarbon analysis system capable of measuring both JP-8 vapor and aerosol concentrations. Pulmonary function and respiratory permeability tests were performed 24 to 30 hr after the final exposures. No significant effects were observed at 45 or 267 mg/m 3 . The only significant effect observed at 406 mg/m 3 was a decrease in inspiratory dynamic lung compliance. Morphological examination and morphometric analysis of distal lung tissue demonstrated that alveolar type II epithelial cells showed limited cellular damage with the notable exception of a significant increase in the volume density of lamellar bodies (vacuoles), which is indicative of increased surfactant production, at 45 and 406 mg/m 3 . The terminal bronchial epithelium showed initial signs of cellular damage, but the morphometric analysis did not quantify these changes as significant. The morphometric analysis techniques appear to provide an increased sensitivity for detecting the deleterious effects of JP-8 as compared to the physiological evidence offered by pulmonary function or respiratory permeability tests. These observations suggest that the current 350 mg/m 3 PEL for both JP-8 jet fuel and for other more volatile petroleum distillates should be reevaluated and a lower, more accurate PEL should be established with regard human occupational exposure limits.

In vivo comparison of epithelial responses for S-8 versus JP-8 jet fuels below permissible exposure limit

“…This method has been duplicated from the previous jet fuel exposure studies performed in our laboratory (Herrin et al, 2006). Both fuel (Syntroleum, Tulsa, OK, USA) vapor/aerosol mixture were generated using a Lovelace jet nebulizer (Model 01–100, IN-TOX, Albuquerque, New Mexico, USA).…”

“…Animals were exposed over a period of seven consecutive days for one hour/day at 53 mg/m 3 (80 ppm THC, Figure 1) concentration for both JP-8 and S-8. The exposure protocol was chosen based on our recent study that initially indicated cellular alterations in terminal airways at this exposure level (Herrin et al, 2006). Control mice were exposed to ambient air for one hour/day each day for seven consecutive days.…”

“…For example, acute 1-hour inhalation exposures to aerosolized JP-8 have been shown to induce cellular and morphological indications of pulmonary toxicity that were associated with increased respiratory permeability to 99mTc-DTPA (Robledo and Witten, 1998). Most recently, morphological examination and morphometric analysis of distal lung tissue demonstrated that alveolar type II epithelial cells showed a notable increase in the volume density of lamellar bodies (vacuoles), which is indicative of increased surfactant production at 45 mg/m 3 (Herrin et al 2006). The morphometric analysis techniques appear to provide an increased sensitivity for detecting the deleterious effects of JP-8 as compared to the evidence offered by physiological and biochemical tests.…”

“…The risks of aerosol plus vapor exposure of less-volatile kerosene-based JP-8 or aliphatic hydrocarbon fuel S-8 were not taken into consideration. Based on our previous dose-effect (45–406 mg/m 3 ) JP-8 study (Herrin et al 2006), the present study was specifically formulated to examine whether toxic effects or lung injury occurred after a low level exposure to S-8 compared to an identical exposure to JP-8 at 53 mg/m 3 for seven consecutive days for one hour/day. The mouse model, established by a simulated flightline exposure protocol, was utilized to examine the effects of both mixtures of jet fuel vapors/aerosols.…”

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

“…At 45 and 406 mg/m 3 , the vacuole volume density of lamellar bodies was increased, which is indicative of increased surfactant production. In addition, detachment of the epithelial cells of the airways was observed that was not dependent on the concentration (Herrin et al 2006).…”