Changes in Absorbance at 413 nm in Plasma from Three Rodent Species Exposed to Phosgene

Sciuto, Alfred M.; Stotts, Richard R.; Chittenden, Valerie; Choung, Edward; Heflin, Matthew D.

doi:10.1006/bbrc.1996.1448

Cited by 16 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased blood flow in areas of already heightened capillary pressure will cause pressure to further increase, thus surpassing the ability of alveolar capillaries to maintain proper fluid balance. In addition, free hemoglobin released from damaged RBC can act as a Fenton reagent and produce highly reactive hydroxyl radicals, further stimulating ROS formation in the alveolar space [14]. …”

Section: 0 Results and Discussionmentioning

confidence: 99%

“…The diffusion length of phosgene in an aqueous solution has been measured to be about 8.8 μm, which is 4–8 times the thickness of the air/blood barrier [13]. The ability of phosgene to enter the capillary circulation following inhalation has been shown [14], thus providing evidence that phosgene can exert toxic effects on tissues, blood, and cellular components throughout the lung. Biologically, acylation and free radical-mediated reactions are the most relevant reactions that occur between phosgene and important cellular constituents.…”

Section: 0 Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Conceptual approaches for treatment of phosgene inhalation-induced lung injury

Holmes¹,

Keyser²,

Paradiso³

et al. 2016

Toxicology Letters

Self Cite

View full text Add to dashboard Cite

Toxic industrial chemicals are used throughout the world to produce everyday products such as household and commercial cleaners, disinfectants, pesticides, pharmaceuticals, plastics, paper, and fertilizers. These chemicals are produced, stored, and transported in large quantities, which poses a threat to the local civilian population in cases of accidental or intentional release. Several of these chemicals have no known medical countermeasures for their toxic effects. Phosgene is a highly toxic industrial chemical which was used as a chemical warfare agent in WWI. Exposure to phosgene causes latent, non-cardiogenic pulmonary edema which can result in respiratory failure and death. The mechanisms of phosgene-induced pulmonary injury are not fully identified, and currently there is no efficacious countermeasure. Here, we provide a proposed mechanism of phosgene-induced lung injury based on the literature and from studies conducted in our lab, as well as provide results from studies designed to evaluate survival efficacy of potential therapies following whole-body phosgene exposure in mice. Several therapies were able to significantly increase 24 hr survival following an LCt50–70 exposure to phosgene; however, no treatment was able to fully protect against phosgene-induced mortality. These studies provide evidence that mortality following phosgene toxicity can be mitigated by neuro- and calcium-regulators, antioxidants, phosphodiesterase and endothelin receptor antagonists, angiotensin converting enzymes, and transient receptor potential cation channel inhibitors. However, because the mechanism of phosgene toxicity is multifaceted, we conclude that a single therapeutic is unlikely to be sufficient to ameliorate the multitude of direct and secondary toxic effects caused by phosgene inhalation.

show abstract

Section: 0 Results and Discussionmentioning

confidence: 99%

Section: 0 Introductionmentioning

confidence: 99%

Conceptual approaches for treatment of phosgene inhalation-induced lung injury

Holmes¹,

Keyser²,

Paradiso³

et al. 2016

Toxicology Letters

Self Cite

View full text Add to dashboard Cite

show abstract

“…In animal studies (guinea pigs, rats, and mice), Sciuto et al (1996) reported that whole-body exposure to phosgene (> 22 ppm, 20 min) resulted in alterations of red blood cell membranes with increased fragility and increased hemolysis. Small amounts of phosgene dissolved in water produce hydrochloric acid, an eye and throat irritant (Borak and Diller 2001); this seems to corroborate the acidic, foul odor that exposed residents reported smelling that night.…”

Section: Discussionmentioning

confidence: 99%

Grand Rounds: Outbreak of Hematologic Abnormalities in a Community of People Exposed to Leakage of Fire Extinguisher Gas

Chan

Chen

et al. 2006

Environ Health Perspect

View full text Add to dashboard Cite

ContextAlthough there are ample data on the respiratory effects of exposure to fire extinguisher gas, the potential hematologic effects have not been fully documented. We conducted this study to determine the possible etiologic agent(s) for a decrease in red blood cells among community residents in Taipei, Taiwan, after they were exposed to leakage of mixed fire extinguishants containing bromotrifluoromethane (CF3Br, Halon 1301), bromochlorodifluoromethane (CF2BrCl, Halon 1211), and dichlorodifluoromethane (CCl2F2, CFC-12).Case presentationWe studied 117 exposed residents who came into one hospital for physical examinations. We also selected age- and sex-matched referents for comparison from residents who came to the same hospital for health examinations. Nine months after the exposure to mixed fire extinguishants, 91 of the exposed residents came back for a second physical examination. In the first examination of the exposed residents, we found a significant reduction in red blood cell count and hemoglobin and a relationship between dose and response.DiscussionAfter excluding iron-deficiency anemia, thalassemia, and other possible agents, we suspected that the hematologic effects might have resulted from pyrolytic products of CFC-12 and Halon 1211, which may contain phosgene, among other products.Relevance to clinical practiceThe acute transient hematologic effects observed in the exposed residents were associated with the incident of leakage of mixed fire-extinguisher gases and were most likely caused by a small amount of pyrolytic products, probably phosgene. Nine months after the exposure, we found a significant improvement in the abnormalities without any specific treatment.

show abstract

“…The reactions include direct damage to lung surfactant and peroxidation of lipids, including membrane phospholipids. [22][23][24][25][26] This damage then leads to the downstream release of arachidonic acid mediators such as the leukotrienes and the upregulation of oxidative response enzymes. 27,28 The chemical changes induced by phosgene inhalation have been shown both in isolated lung preparations, in animal models and in human cases to cause increases in vascular permeability, alveolar leakage, and pulmonary edema.…”

Section: Pathophysiologymentioning

confidence: 99%