Publication Cover
Inhalation Toxicology
International Forum for Respiratory Research
Volume 19, 2007 - Issue 10
235
Views
67
CrossRef citations to date
0
Altmetric
Research Article

Workshop Summary: Phosgene-Induced Pulmonary Toxicity Revisited: Appraisal of Early and Late Markers of Pulmonary Injury From Animal Models With Emphasis on Human Significance

, , , , , , , & show all
Pages 789-810 | Received 03 Mar 2007, Accepted 12 Apr 2007, Published online: 06 Oct 2008

REFERENCES

  • AEGL. AEGL (acute exposure guideline levels) for selected airborne chemicals, Volume 2, 2002. Phosgene. National Academies Press, Washington, DC 2004, Prepared by the National Research Council of the National Academies
  • Albert R., Lakshminarayan K. S., Hildebrandt J., Kirk W., Butler J. Increased surface tension favors pulmonary edema formation in anesthetized dogs' lungs. J. Clin. Invest. 1979; 63: 1015–1018
  • Amis T. C., O'Neill N., Van der Touw T., Brancatisano A. Mechanisms of oronasal airflow partitioning in dogs. Respir. Physiol. 1996; 104: 169–177
  • Bauer R. M., Young G. D., Keeler J. R. Tachykinins and pulmonary edema after acute phosgene exposure in guinea pigs. J. Am. Coll. Toxicol. 1997; 15: S99–S112, (suppl. 2)
  • Berthiaume Y., Staub N. C., Matthay M. A. Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep. J. Clin. Invest. 1987; 79: 335–343
  • Berthiaume Y. Mechanisms of edema clearance. Pulmonary edema, E. K. Weir, J. T. Reeves. Futura, Armonk, NY 1998; 77–94
  • Berthiaume Y., Lesur O., Dagenais A. Treatment of adult respiratory distress syndrome: Plea for rescue therapy of the alveolar epithelium. Thorax 1999; 54: 150–160
  • Berthiaume Y., Folkesson H. G., Matthay M. A. Lung edema clearance: 20 Years of progress—Invited review: Alveolar edema fluid clearance in the injured lung. J. Appl. Physiol. 2002; 93: 2207–2213
  • Bide R. W., Armour S. J., Yee E. Allometric respiration/body mass data for animals to be used for estimates of inhalation toxicity to young adult humans. J. Appl. Toxicol. 2000; 20: 273–290
  • Bide R. W., Armour S. J., Yee E. GB toxicity reassessed using newer techniques for estimation of human toxicity from animal inhalation toxicity data: New method for estimating acute human toxicity. J. Appl. Toxicol. 2005; 25: 393–409
  • Borak J., Diller W. F. Phosgene exposure: Mechanisms of injury and treatment strategies. J. Occup. Environ. Med. 2000; 43: 110–119
  • Boyd E. M. Antidotes for phosgene-induced pulmonary edema. J. Pharm. Pharmacol. 1969; 21: 557
  • Boyd E. M., Perry W. F. Postural drainage of respiratory tract fluid in phosgene-induced pulmonary edema. J. Pharm. Pharmacol. 1963; 15: 466–471
  • Bredenberg C. E., Nieman G. E., Paskanik A. M., Hart A. K. E. Microvascular membrane permeability in high surface tension pulmonary edema. Appl. Physiol. 1986; 60: 253–259
  • Brown R. F. R., Jugg B. J. A., Harban F. M. J., Ashley Z., Kenward C. E., Platt K. J., Hill A., Rice P., Watkins P. E. Pathophysiological responses following phosgene exposure in the anaesthetized pig. J. Appl. Toxicol. 2002; 22: 263–269
  • Cameron G. R., Courtice F. C. The production and removal of oedema fluid in the lung after exposure to carbonyl chloride (phosgene). J. Physiol. 1946; 105: 175–185
  • Castranova V., Rabovsky J., Tucker J. H., Miles P. R. The alveolar type II epithelial cell: A multifunctional pneumocyte. Toxicol. Appl. Pharmacol. 1988; 93: 472–473
  • Chan A., Berry L., O'Brodovich H., Klement P., Mitchell L., Baranowski B., Monagle P., Andrew M. Covalent antithrombin–heparin complexes with high anticoagulant activity. J. Biol. Chem. 1997; 272: 22111–22117
  • Collins J. F., Alexeeff G. V., Lewis D. C., Dodge D. E., Marty M. A., Parker T. R., Budroe J. D., Lam R. H. F., Lipsett M. J., Fowles J. R., Das R. Development of acute inhalation reference exposure levels (RELs) to protect the public from predictable excursions of airborne toxicants. J. Appl. Toxicol. 2004; 24: 155–166
  • Crouch E., Wright J. R. Surfactant proteins A and D and pulmonary host defense. Annu. Rev. Physiol. 2001; 63: 521–554
  • Cucinell S. A., Edgewood A. Review of the toxicity of long-term phosgene exposure. Arch. Environ. Health 1974; 28: 272–275
  • Currie W. D., Pratt P. C., Frosolono M. F. Response of pulmonary energy metabolism to phosgene. Toxicol. Ind. Health 1985; 1(2)17–27
  • Currie W. D., Hatch G. E., Frosnolo M. F. Changes in lung ATP concentrations in the rat after low-level phosgene exposure. J. Biochem. Toxicol. 1987a; 2: 105–114
  • Currie W. D., Hatch G. E., Frosnolo M. F. Pulmonary alterations in rats due to acute phosgene inhalation. Fundam. Appl. Toxicol. 1987b; 8: 107–114
  • Darmer K. I., Kinkead E. R., DiPasquale L. C. Acute toxicity in rats and mice exposed to hydrogen chloride gas and aerosols. Am. Ind. Hyg. Assoc. J. 1974; 35: 623–331
  • DeGeorge J. J., Ahn C. H., Andrews P. A., Brower M. E., Choi Y. S., Chun M. Y., Du T., Lee-Ham D. Y., McGuinn W. D., Pei L., Sancilio L. F., Schmidt W., Sheevers H. V., Sun C. J., Tripathi S., Vogel W. M., Whitehurst V., Williams S., Taylor A. S. Considerations for toxicology studies of respiratory drug products. Regul. Toxicol. Pharmacol. 1997; 25: 189–193
  • Deshpande A., Archuleta D. C., Valdez Y. E., Lehnert N. M., Stavert D. M., Lehnert B. E. Tumor necrosis factor-α production by alveolar macrophages during the early development of phosgene-induced lung injury. Inhal. Toxicol. 1996; 8: 65–80
  • Diller W. F., Zante R. Dosis-Wirkungs-Beziehungen bei Phosgen-Einwirkung auf Mensch und Tier. Zbl. Arbeitsmed. 1982; 32: 360–36
  • Diller W. F. Pathogenesis of phosgene poisoning. Toxicol. Ind. Health 1985a; 1: 7
  • Diller W. F. Late sequelae after phosgene poisoning: A literature review. Toxicol. Ind. Health 1985b; 1: 129–133
  • Diller W. F., Bruch J., Dehnen W. Pulmonary changes in the rat following low phosgene exposure. Arch. Toxicol. 1985; 57: 184–190
  • Doyle I. R., Nicholas T. E., Bersten A. D. Partitioning lung and plasma protein: Circulating surfactant proteins as biomarkers of alveolocapillary permeability. Clin. Exp. Pharmacol. Physiol. 1999; 26: 185–197
  • Drake R. E., Laine G. A., Allen S. J., Katz J., Gabel J. C. A model of the lung interstitial-lymphatic system. Microvasc. Res. 1987; 34: 96–107
  • Duniho S. M., Martin J., Forster J. S., Cascio M. B., Moran T. S., Carpin L. B., Sciuto A. M. Acute pulmonary changes in mice exposed to phosgene. Toxicol. Pathol. 2002; 30: 339–349
  • Durlacher S. H., Bunting H. Pulmonary changes following exposure to phosgene. Am. J. Pathol. 1947; 23: 679–693
  • Fehrenbach H. Alveolar epithelial type II cell: Defender of alveolus revisited. Respir. Res. 2001; 2: 33–46
  • Folkesson H. G., Matthay M. A., Weström B. R., Kim K. J., Karlsson B. W., Hastings R. H. Alveolar epithelial clearance of protein. J. Appl. Physiol. 1996; 80: 1431–1445
  • Franch S., Hatch G. E. Pulmonary biochemical effects of inhaled phosgene. J. Toxicol. Environ. Health 1986; 19: 413–423
  • Frank J. A., Wang Y., Osorio O., Matthay M. A. β-Adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats. J. Appl. Physiol. 2000; 89: 1255–1265
  • Frosolono M. F., Pawlowski R. Effect of phosgene on rat lungs after single high-level exposure: I. Biochemical alterations. Arch. Environ. Health 1977; 32: 271–277
  • Frosolono M. F., Curry W. D. Response of the pulmonary surfactant system to phosgene. Toxicol. Ind. Health 1985; 1: 29–35
  • Gerriets J. E., Reiser K. M., Last J. A. Lung collagen crosslinks in rats with experimentally induced pulmonary fibrosis. Biochim. Biophys. Acta 1996; 1316: 121–131
  • Ghio A. J., Lehmann J. R., Winsett D. W., Richards J. H., Costa D. L. Colchicine decreases airway hyperreactivity after phosgene exposure. Inhal. Toxicol. 2005; 17: 277–285
  • Gilmour M. I., Selgrade M. J. A comparison of the pulmonary defenses against streptococcal infection in rats and mice following O3 exposure: Differences in disease susceptibility and neutrophil recruitment. Toxicol. Appl. Pharmacol. 1993; 123: 211–218
  • Guidot D. M., Folkesson H. G., Jain L., Sznajder J. I., Pittet J.-F., Matthay M. A. Integrating acute lung injury and regulation of alveolar fluid clearance. Am. J. Physiol. Lung Cell Mol Physiol. 2006; 291: L301–L306
  • Gross P., Rinehart W. E., Hatch T. Chronic pneumonitis caused by phosgene. Arch. Environ. Health 1965; 10: 768–775
  • Günther A., Lübke N., Ermert M., Schermuly R. T., Weissmann N., Breithecker A., Markart P., Ruppert C., Quanz K., Ermert L., Grimminger F., Seeger W. Prevention of bleomycin-induced lung fibrosis by aerosolization of heparin or urokinase in rabbits. Am. J. Respir. Crit. Care Med. 2003; 168: 1358–1365
  • Hakkinen P. J., Witschi H. P. Animal models. Toxicology of inhaled materials: General principles of inhalation toxicology, H. P. Witschi, J. D. Brain. Springer-Verlag, New York 1985; 95–114, Handbook of Experimental Pharmacology, vol. 75
  • Haque R., Umstead T. M., Ponnuru P., Guo X., Hawgood S., Phleps D. S., Floros J. Role of surfactant protein-A (SP-A) in lung injury in response to acute ozone exposure of SP-A deficient mice. Toxicol. Appl. Pharmacol. 2007; 220: 72–82
  • Hatch G. E. Comparative biochemistry of airway lining fluid. Treatise on pulmonary toxicology—Comparative biology of the normal lung, R. A. Parent. CRC Press, Boca Raton, FL 1992; Vol. I: 617–632
  • Hatch G. E., Slade R., Stead A. G., Graham J. A. Species comparison of acute inhalation toxicity of ozone and phosgene. J. Toxicol. Environ. Health 1986; 19: 43–53
  • Hatch G. E., Kodavanti U., Crissman K., Slade R., Costa D. An “injury-time integral” model for extrapolating from acute to chronic effects of phosgene. Toxicol. Ind. Health 2001; 17: 285–293
  • Heyder J., Takenaka S. Long-term canine exposure studies with ambient air pollutants. Eur. Respir. J. 1996; 9: 571–584
  • Hills B. A. An alternative view of the role(s) of surfactant and the alveolar model. J. Appl. Physiol. 1999; 87: 1567–1583
  • Howell D. C., Laurent G. J., Chambers R. C. Role of thrombin and its major cellular receptor, protease-activated receptor-I, in pulmonary fibrosis. Biochem. Society Trans. 2002; 30: 211–216, (part 2)
  • IPCS. Phosgene—Health and safety guide no. 106. 1998, http://inchem.org.documents/hsg/hsg/hsg106.htm
  • Jugg B., Jenner J., Rice P. The effect of perfluoroisobutene and phosgene on rat lavage fluid surfactant phospholipids. Hum. Exp. Toxicol. 1999; 18: 659–668
  • Kaplan J., Koehler R. C., Terry P. B., Menkes H. A., Traystman R. J. Effect of lung volume on collateral ventilation in the dog. J. Appl. Physiol. Respirat. Environ. Exercise Physiol. 1980; 49: 9–15
  • Keeler J. R., Hurt H. H., Nold J. B., Corcoran K. D., Tezak-Reid T. M. Phosgene-induced lung injury in sheep. Inhal. Toxicol. 1990a; 2: 391–406
  • Keeler J. R., Hurt H. H., Nold J. B., Lennox W. J. Estimation of the LC50 of phosgene in sheep. Drug Chem. Toxicol. 1990b; 13: 229–239
  • Kennedy T. P., Michael R., Hoidal J. R., Hasty D., Sciuto A. M., Hopkins C., Lazar R., Bysani G. K., Tolley E., Gurtner G. H. Dibutyl cAMP, aminophylline, and β-adrenergic agonists protect against pulmonary edema caused by phosgene. J. Appl. Physiol. 1989; 67: 2542–2552
  • Kodavanti U. P., Costa D. L., Giri S. N., Starcher B., Hatch G. E. Pulmonary structural and extracellular matrix alterations in Fischer 344 rats following subchronic exposure. Fundam. Appl, Toxicol. 1997; 37: 54–63
  • Kreyling W. G., Dirscherl P., Ferron G. A., Heilmann P., Josten M., Miaskowski U., Neuner M., Ruprecht L., Schumann G., Tabenaka S., Ziesenis A., Heyder J. Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities. Inhal. Toxicol. 1999; 11: 391–422
  • Lailey A. F., Hill L., Lawston I. W., Stanton D., Upshall D. G. Protection by cysteine esters against chemically induced pulmonary edema. Biochem. Pharmacol. 1991; 42: S47–S54
  • Last J. A. Biochemical and cellular interrelationships in the development of ozone-induced pulmonary fibrosis. Air pollution, the automobile and public health, R. Bates. National Academy of Sciences, Washington, DC 1988; 415–440
  • Last J. A., Greenberg D. B. Ozone-induced alterations in collagen metabolism of rat lungs. Toxicol. Appl. Pharmacol. 1980; 55: 108–114
  • Last J. A., Reiser K. M., Tyler W. S., Rucker R. B. Long-term consequences of exposure to ozone. Toxicol. Appl. Pharmacol. 1984; 72: 111–118
  • Last J. A. Changes in the collagen pathways in fibrosis. Fundam. Appl. Toxicol. 1985; 5: 210–218
  • Last J. A., Wu R., Chen J., Gelzleichter T., Sun W., Armstrong L. G. Particle–cell interactions: Lung fibrogenesis. J. Aerosol Med. 1990; 3: S61–S74
  • Lee L.-Y., Widdicombe J. G. Modulation of airway sensitivity to inhaled irritants: Role of inflammatory mediators. Environ. Health Perspect. 2001; 109: 585–589, (suppl. 4)
  • Li W.-L., Hai C.-X., Liang X., Zhang X.-D., Chen H.-L., Qin X.-J., Liu R., He W., Wang P., Li B. Apoptosis of ATII cells in mice induced by phosgene. Inhal. Toxicol. 2006; 18: 71–77
  • Lum H., Mitzner W. A species comparison of alveolar size and surface forces. J. Appl. Physiol. 1987; 62: 1865–1871
  • Madden M. C., Friedman M., Keyes L., Koren H. S., Burleson G. R. Effects of phosgene exposure on lung arachidonic acid metabolism. Inhal. Toxicol. 1991; 3: 73–90
  • Matthay M. A., Clerici C., Saumon G. Lung Edema Clearance: 20 Years of Progress. Invited reviews: Active fluid clearance from the distal air spaces of the lung. J. Appl. Physiol. 2002a; 93: 1533–1541
  • Matthay M. A., Folkesson H. G., Clerici C. Lung epithelial fluid transport and resolution of pulmonary edema. Physiol. Rev. 2002b; 82: 569–600
  • Mautone A. J., Katz Z., Scarpelli E. M. Acute responses to phosgene inhalation and selected corrective measures (including surfactant). Toxicol. Ind. Health 1985; 1: 37–55
  • Menkes H., Traystman R., Terry P. Collateral ventilation. Fed. Proc. 1979; 38: 22–26
  • Nash T., Pattle R. E. The absorption of phosgene by aqueous solutions and its relation to toxicity. Ann. Occup. Hyg. 1971; 14: 227–333
  • National Research Council. Standing operating procedures for developing acute exposure guideline levels for hazardous chemicals. National Academy Press, Washington, DC 2001
  • Nieman G. F. Current concepts of lung-fluid balance. Respir. Care 1985; 30: 1062–1076
  • Okonek S., Schuster S., Löser E., Pauluhn J. Hämodynamik und biochemische Veränderungen im toxischen Lungenödem durch Phosgen. MuP–Hefte 1987; 36–44, 1/1987
  • Paintal A. S. Mechanism of stimulation of type J receptors. J. Physiol. 1969; 203: 511–532
  • Paintal A. S. Effects of drugs on chemoreceptors, pulmonary and cardiovascular receptors. International encyclopedia of pharmacology and therapeutics, J. G. Widdicombe. Pergamon Press, Oxford 1981; 217–239, Section 104, Respiratory pharmacology
  • Pawlowski R., Frosolono M. F. Effect of phosgene on rat lungs after single high-level exposure. II. Ultrastructural alternations. Arch. Environ. Health 1977; 32(6)278–283
  • Park S. S., Kikkawa Y., Goldring I. P., Daly M. M., Zelefsky M., Shim C., Spierer M., Morita T. An animal model of cigarette smoking in beagle dogs: Correlative evaluation of effects on pulmonary function, defense, and morphology. Am. Rev. Respir. Dis. 1977; 115: 971–979
  • Parker J. C., Townsley M. I. Evaluation of lung injury in rats and mice. Am. J. Physiol. Lung Cell Mol. Physiol. 2004; 286: L231–L246
  • Pauluhn J., Mohr U. Inhalation studies in laboratory animals—Current concepts and alternatives. Review. Toxicol Pathol 2000; 28: 734–753
  • Pauluhn J. Acute inhalation toxicity of polymeric diphenyl-methane-4,4′-diisocyanate (MDI) in rats: Time course of changes in bronchoalveolar lavage. Arch. Toxicol. 2000a; 74: 257–269
  • Pauluhn J. Inhalation toxicity of 1,6-hexamethylene diisocyanate-homopolymer (HDI-IC) aerosol: Results of single inhalation exposure studies. Toxicol. Sci. 2000b; 58: 173–181
  • Pauluhn J. Short-term inhalation toxicity of polyisocyanate aerosols in rats: Comparative assessment of irritant-threshold concentrations by bronchoalveolar lavage. Inhal. Toxicol. 2002a; 14: 287–301
  • Pauluhn J. Critical analysis of biomonitoring endpoints for measuring exposure to polymeric diphenyl-methane-4,4′-diisocyanate (MDI) in rats: A comparison of markers of exposure and markers of effect. Arch. Toxicol. 2002b; 76: 13–22
  • Pauluhn J. Pulmonary irritant potency of polyisocyanate aerosols in rats: Comparative assessment of irritant-threshold concentrations by bronchoalveolar lavage. J. Appl. Toxicol. 2004a; 24: 231–247
  • Pauluhn J. Comparative analysis of pulmonary irritation by measurements of Penh and protein in bronchoalveolar lavage fluid in Brown Norway rats and Wistar rats exposed to irritant aerosols. Inhal. Toxicol. 2004b; 16: 159–175
  • Pauluhn J. Acute nose-only exposure of rats to phosgene. Part I: Concentration × time dependence of LC50s and non-lethal-threshold concentrations and analysis of breathing patterns. Inhal. Toxicol. 2006a; 18: 423–435
  • Pauluhn J. Acute nose-only exposure of rats to phosgene. Part II: Concentration × time dependence of changes in bronchoalveolar lavage during a follow-up period of 3 months. Inhal. Toxicol. 2006b; 18: 595–607
  • Pauluhn J. Acute head-only exposure of dogs to phosgene. Part III: Comparison of indicators of lung injury in dogs and rats. Inhal. Toxicol. 2006c; 18: 609–621
  • Persson C. G. A., Erjefält J. S., Andersson M., Greiff L., Svensson C. Extravasation, lamina propria flooding and luminal entry of bulk plasma exudates in mucosal defence, inflammation and repair. Pulmon. Pharmacol. 1996; 9: 129–139
  • Pinkerton K. E., Gehr P., Crapo J. D. Architecture and cellular composition of the air–blood barrier. Treatise on pulmonary toxicology—Comparative biology of the normal lung (Vol. I), R. A. Parent. CRC Press, Boca Raton, FL 1992; 121–128
  • Pittet J. F., Mackersie R. C., Martin T. R., Matthay M. A. Biological markers of acute lung injury: Prognostic and pathogenetic significance. Am. J. Respir. Crit. Care Med. 1997; 155: 1187–1205
  • Putman E., van Golde M., Haagsman H. P. Toxic oxidant species and their impact on the pulmonary surfactant system. Lung 1997; 175: 75–103
  • Reidy M. F., Wright J. R. Surfactant protein A enhances apoptotic cell uptake and TGF-beta1 release by inflammatory alveolar macrophages. Am. J. Physiol. Lung Cell. Moll. Physiol. 2003; 285: L854–L861
  • Ribeiro-Gomes F. L., Otero A. C., Gomes N. A., Moniz-de-Souza M. C. A., Cysne-Finkelstein L., Arnholdt A., Calich V. L., Coutinho S. G., Lopes M. F., DosReis G. A. Macrophage interactions with neutrophils regulate Leishmania major infection. J. Immunol. 2004; 172: 4454–4462
  • Richards R. J., Masek L. C., Brown F. R. Biochemical and cellular mechanisms of pulmonary fibrosis. Toxicol. Pathol. 1991; 19: 526–539
  • Rinehart W. E., Hatch T. Concentration–time product (CT) as an expression of dose in sublethal exposures to phosgene. Am. Ind. Hyg. Assoc. J. 1964; 25: 545–553
  • Rosiello A. P., Essigmann J. M., Wogan G. N. Rapid and accurate determination of the median lethal dose (LD50) and its error with small computer. J. Toxicol. Environ. Health 1977; 3: 797–809
  • Ruppert C., Markart P., Schmidt R., Grimminger F., Seeger W., Lehr C.-M., Günther A. Chemical crosslinking of urokinase to pulmonary surfactant protein B for targeting alveolar fibrin. Thromb. Haemostasis 2003; 89: 53–64
  • Sciuto A. M. Ibuprofen treatment enhances the survival of mice following exposure to phosgene. Inhal. Toxicol. 1997; 9: 389–403
  • Sciuto A. M. Assessment of early acute lung injury in rodents exposed to phosgene. Arch. Toxicol 1998; 72: 283–288
  • Sciuto A. M., Hurt H. H. Therapeutic treatments of phosgene-induced lung injury. Inhal. Toxicol. 2004; 16: 565–580
  • Sciuto A. M., Strickland P. T., Kennedy T. P., Gurtner G. H. Protective effects of N-acetylcysteine treatment after phosgene exposure in rabbits. Am. J. Respir. Crit. Care Med. 1995; 151: 768–772
  • Sciuto A. M., Strickland P. T., Kennedy T. P., Guo Y.-L., Gurtner G. H. Intratracheal administration of DBcAMP attenuates edema formation in phosgene-induced acute pulmonary injury. J. Apppl. Physiol. 1996; 80: 149–157
  • Sciuto A. M., Lee R. B., Forster J. S., Cascio M. B., Clapp D. L., Moran T. S. Temporal changes in respiratory dynamics in mice exposed to phosgene. Inhal. Toxicol. 2002; 14: 487–501
  • Sciuto A. M., Cascio M. B., Moran T. S., Forster J. S. The fate of antioxidant enzymes in bronchoalveolar lavage fluid over 7 days in mice with acute lung injury. Inhal. Toxicol. 2003a; 15: 675–685
  • Sciuto A. M., Carpin L. B., Moran T. S., Forster J. S. Chronological changes in electrolyte levels in arterial blood and bronchoalveolar lavage fluid in mice after exposure to an edemagenic gas. Inhal. Toxicol. 2003b; 15: 663–674
  • Sciuto A. M., Clapp D. L., Hess Z. A., Moran T. S. The temporal profile of cytokines in the bronchoalveolar lavage fluid in mice exposed to the industrial gas phosgene. Inhal. Toxicol. 2003c; 15: 687–700
  • Sciuto A. M., Phillips C. S., Orzolek L. D., Hege A. I., Moran T. S., Dillman J. F. Genomic analysis of murine pulmonary tissue following carbonyl chloride inhalation. Chem. Res. Toxicol. 2005; 18: 1654–1660
  • Schroeder S., Gurtner G. H. Evidence for a species difference in susceptibility and mechanism of phosgene toxicity between rabbits and dogs. Am. Rev. Respir. Dis. 1992; 145: A606, (part II)
  • Seeger W., Stöhr G., Wolf H. R. D., Neuhof H. Alteration in surfactant function due to protein leakage: Special interaction with fibrin monomer. J. Appl. Physiol. 1985; 58: 326–338
  • Selgrade M. K., Starnes D. M., Illing J. W., Daniels M. J., Graham J. A. Effects of phosgene exposure on bacterial, viral, and neoplastic lung disease susceptibility in mice. Inhal. Toxicol. 1989; 1: 243–259
  • Selgrade M. K., Gilmour M. I., Yang Y. G., Burleson G. R., Hatch G. E. Pulmonary host defenses and resistance to infection following subchronic exposure to phosgene. Inhal. Toxicol. 1995; 7: 1257–1268
  • Slade R., Crissman K., Norwood J., Hatch G. Comparison of antioxidant substances in bronchoalveolar lavage cells and fluid from humans, guinea pigs, and rats. Exp. Lung Res. 1993; 19: 469–484
  • Staub N. C. Pulmonary edema. Physiol. Rev. 1974; 54: 678–811
  • Takenaka S., Heini A., Ritter B., Heyder J. The respiratory bronchiole of beagle dogs: Structural characteristics. Toxicol Lett. 1998; 96–97: 301–308
  • Takenaka S., Heini A., Ritter B., Heyder J. Morphometric evaluation of bronchial glands of beagle dogs. Toxicol Lett. 1996; 88: 279–285
  • ten Berge W. F., Zwart A. More efficient use of animals in acute inhalation toxicity testing. J. Hazard. Mater. 1989; 21: 65–71
  • Thannickal V. J., Toews G. B., White E. S., Lynch J. P., Martinez F. J. Mechanisms of pulmonary fibrosis. Annu. Rev. Med. 2004; 55: 395–417
  • U.S. Environmental Protection Agency. Toxicological review of phosgene. In support of summary information on the Integrated Risk Information System (IRIS). 2005, www.epa.gov/iris EPA/635/R-06/001 available at
  • Vandivier R. W., Ogden C. A., Fadok V. A., Hoffmann P. R., Brown K. K., Botto M., Walport M. J., Fisher J. H., Henson P. M., Greene K. E. Role of surfactant proteins A, D, and C1q in the clearance of apoptotic cells in vivo and in vitro: Calreticulin and CD91 as a common collectin receptor complex. J. Immunol. 2002; 169: 3978–3986
  • van Helden H. P. M., van de Meent D., Oostdijk J. P., Joosen M. J. A., van Esch J. H. M., Hammer A. H., Diemel R. V. Protection of rats against perfluoroisobutene (PFIB)-induced pulmonary edema by curosurf and N-acetylcysteine. Inhal. Toxicol. 2004; 16: 549–564
  • Wang L., Scabilloni J. F., Antonini J. M., Castranova V., Rojanasakul Y., Roberts J. R., Zhang Z., Mercer R. R. Role of lung surfactant in phagocytic clearance of apoptotic cells by macrophages in rats. Lab. Invest. 2006; 86: 458–466
  • Ward P. A., Hunninghake G. W. Lung inflammation and fibrosis. Am. J. Respir. Crit. Care Med. 1998; 157: S123–S129
  • Ware L. B., Matthay M. A. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 2001; 163: 1376–1383
  • Werrlein R. J., Madren-Whalley J. S., Kirby S. D. Phosgene effects on F-actin organization and concentration in cells cultured from sheep and rat lung. Cell Biol. Toxicol. 1994; 19: 45–58
  • Winternitz M. C. Pathology of war gas poisoning. Yale University Press, New Haven, CT 1920; 35–66
  • Witschi H. P., Tryka A. F., Lindenschmidt R. C. The many faces of an increase in lung collagen. Fundam. Appl. Toxicol. 1985; 5: 240–250
  • Wright J. R. Pulmonary surfactant. A front line of lung host defense. J. Clin. Invest. 2003; 111: 1453–1455
  • Yang Y. G., Gilmour M. I., Lange R., Burleson G. R., Selgrade M. K. Effects of acute exposure to phosgene on pulmonary resistance to infection. Inhal. Toxicol. 1995; 7: 393–404
  • Zwart A., Arts J. H. E., Klokman-Houweling J. M., Schoen E. D. Determination of concentration-time-mortality relationships to replace LC50 values. Inhal. Toxicol. 1990; 2: 105–117

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.