Changes in lung permeability correlate with lung histology in a chronic exposure model

A. M. Hays, G. Parliman, J. K. Pfaff, R. C. Lantz, J. Tinajero, Robert Clark Lantz, J. N. Hall, M. L. Witten

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

In a simulated military flight-line exposure protocol, the effects of JP- 8 jet fuel exposure on lung epithelial permeability were evaluated in male Fischer 344 rats (F344). Exposures were nose-only and for one hour daily. Groups were exposed for 7, 28, and 56 days. A protocol for administering a low dose (500mg/m3/hr) and a high dose (813-1094mg/m3/hr) of JP-8 jet fuel was used. Longitudinal sham-exposure groups (no jet fuel) for 7, 28, and 56 days were included in the protocol. Lung epithelial permeability was measured by clearance of technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, molecular weight = 492 daltons, physical half-life = 6.02 hours). The percent clearance of 99mTcDTPA per minute was calculated. Alveolar epithelial clearance for JP-8-exposed rats was dependent on both exposure concentration and duration. It was noted that at low-dose exposure concentrations alveolar epithelial clearance of 99mTcDTPA returned to low levels (LD56 = 1.09% per min; LC56 = 0.98% per min), suggesting recovery as evidenced by microscopic exam. The corresponding 56-day high-dose group (n = 10) had a significantly higher (p < 0.05) value of 2.25% per minute. The 28- day low-dose (n = 15) and high-dose (n = 20) groups had clearance values that were significantly increased from their longitudinal control group (n = 17). The alveolar epithelial permeability values were 2.51, 1.95, and 1.20, respectively. The seven-day longitudinal control, low-dose, and high-dose groups had alveolar permeability values of 1.57, 2.16, and 2.07, respectively. The lung histology correlated with the clearance values. Electron micrographs showed that all groups had interstitial edema resulting from endothelial damage. There was apparent thickening of the alveolar septa, and alveolar macrophages were activated in all groups. Lung permeability data, as determined by 99mTcDTPA alveolar clearance, indicated that lung injuries peaked at 28 days of jet fuel exposure, and this finding corresponded with the histology data. There was a discrepancy in the seven- day group between the number of cells and the 99mTcDTPA clearance values. The HD7 group had a total cell count significantly higher than all other groups, but the 99mTcDTPA clearance values in that group were trot significantly different from that of any other group.

Original languageEnglish (US)
Pages (from-to)325-336
Number of pages12
JournalToxicology and Industrial Health
Volume11
Issue number3
StatePublished - 1995

Fingerprint

Longitudinal control
Histology
Jet fuel
Rats
Permeability
Lung
Technetium
Molecular weight
Recovery
Cell Count
Electrons
Inbred F344 Rats
Alveolar Macrophages
Lung Injury
Nose
Half-Life
Edema
Molecular Weight
JP8 aviation fuel
Control Groups

Keywords

  • diethylenetriamine pentaacetate (TcDTPA)
  • jet fuel
  • JP-8

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health
  • Toxicology

Cite this

Hays, A. M., Parliman, G., Pfaff, J. K., Lantz, R. C., Tinajero, J., Lantz, R. C., ... Witten, M. L. (1995). Changes in lung permeability correlate with lung histology in a chronic exposure model. Toxicology and Industrial Health, 11(3), 325-336.

Changes in lung permeability correlate with lung histology in a chronic exposure model. / Hays, A. M.; Parliman, G.; Pfaff, J. K.; Lantz, R. C.; Tinajero, J.; Lantz, Robert Clark; Hall, J. N.; Witten, M. L.

In: Toxicology and Industrial Health, Vol. 11, No. 3, 1995, p. 325-336.

Research output: Contribution to journalArticle

Hays, AM, Parliman, G, Pfaff, JK, Lantz, RC, Tinajero, J, Lantz, RC, Hall, JN & Witten, ML 1995, 'Changes in lung permeability correlate with lung histology in a chronic exposure model', Toxicology and Industrial Health, vol. 11, no. 3, pp. 325-336.
Hays, A. M. ; Parliman, G. ; Pfaff, J. K. ; Lantz, R. C. ; Tinajero, J. ; Lantz, Robert Clark ; Hall, J. N. ; Witten, M. L. / Changes in lung permeability correlate with lung histology in a chronic exposure model. In: Toxicology and Industrial Health. 1995 ; Vol. 11, No. 3. pp. 325-336.
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abstract = "In a simulated military flight-line exposure protocol, the effects of JP- 8 jet fuel exposure on lung epithelial permeability were evaluated in male Fischer 344 rats (F344). Exposures were nose-only and for one hour daily. Groups were exposed for 7, 28, and 56 days. A protocol for administering a low dose (500mg/m3/hr) and a high dose (813-1094mg/m3/hr) of JP-8 jet fuel was used. Longitudinal sham-exposure groups (no jet fuel) for 7, 28, and 56 days were included in the protocol. Lung epithelial permeability was measured by clearance of technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, molecular weight = 492 daltons, physical half-life = 6.02 hours). The percent clearance of 99mTcDTPA per minute was calculated. Alveolar epithelial clearance for JP-8-exposed rats was dependent on both exposure concentration and duration. It was noted that at low-dose exposure concentrations alveolar epithelial clearance of 99mTcDTPA returned to low levels (LD56 = 1.09{\%} per min; LC56 = 0.98{\%} per min), suggesting recovery as evidenced by microscopic exam. The corresponding 56-day high-dose group (n = 10) had a significantly higher (p < 0.05) value of 2.25{\%} per minute. The 28- day low-dose (n = 15) and high-dose (n = 20) groups had clearance values that were significantly increased from their longitudinal control group (n = 17). The alveolar epithelial permeability values were 2.51, 1.95, and 1.20, respectively. The seven-day longitudinal control, low-dose, and high-dose groups had alveolar permeability values of 1.57, 2.16, and 2.07, respectively. The lung histology correlated with the clearance values. Electron micrographs showed that all groups had interstitial edema resulting from endothelial damage. There was apparent thickening of the alveolar septa, and alveolar macrophages were activated in all groups. Lung permeability data, as determined by 99mTcDTPA alveolar clearance, indicated that lung injuries peaked at 28 days of jet fuel exposure, and this finding corresponded with the histology data. There was a discrepancy in the seven- day group between the number of cells and the 99mTcDTPA clearance values. The HD7 group had a total cell count significantly higher than all other groups, but the 99mTcDTPA clearance values in that group were trot significantly different from that of any other group.",
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AU - Pfaff, J. K.

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AU - Tinajero, J.

AU - Lantz, Robert Clark

AU - Hall, J. N.

AU - Witten, M. L.

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N2 - In a simulated military flight-line exposure protocol, the effects of JP- 8 jet fuel exposure on lung epithelial permeability were evaluated in male Fischer 344 rats (F344). Exposures were nose-only and for one hour daily. Groups were exposed for 7, 28, and 56 days. A protocol for administering a low dose (500mg/m3/hr) and a high dose (813-1094mg/m3/hr) of JP-8 jet fuel was used. Longitudinal sham-exposure groups (no jet fuel) for 7, 28, and 56 days were included in the protocol. Lung epithelial permeability was measured by clearance of technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, molecular weight = 492 daltons, physical half-life = 6.02 hours). The percent clearance of 99mTcDTPA per minute was calculated. Alveolar epithelial clearance for JP-8-exposed rats was dependent on both exposure concentration and duration. It was noted that at low-dose exposure concentrations alveolar epithelial clearance of 99mTcDTPA returned to low levels (LD56 = 1.09% per min; LC56 = 0.98% per min), suggesting recovery as evidenced by microscopic exam. The corresponding 56-day high-dose group (n = 10) had a significantly higher (p < 0.05) value of 2.25% per minute. The 28- day low-dose (n = 15) and high-dose (n = 20) groups had clearance values that were significantly increased from their longitudinal control group (n = 17). The alveolar epithelial permeability values were 2.51, 1.95, and 1.20, respectively. The seven-day longitudinal control, low-dose, and high-dose groups had alveolar permeability values of 1.57, 2.16, and 2.07, respectively. The lung histology correlated with the clearance values. Electron micrographs showed that all groups had interstitial edema resulting from endothelial damage. There was apparent thickening of the alveolar septa, and alveolar macrophages were activated in all groups. Lung permeability data, as determined by 99mTcDTPA alveolar clearance, indicated that lung injuries peaked at 28 days of jet fuel exposure, and this finding corresponded with the histology data. There was a discrepancy in the seven- day group between the number of cells and the 99mTcDTPA clearance values. The HD7 group had a total cell count significantly higher than all other groups, but the 99mTcDTPA clearance values in that group were trot significantly different from that of any other group.

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