Chlorine Gas Inhalation: Human Clinical Evidence of Toxicity and Experience in Animal Models

White, Carl W.; Martin, James G.

doi:10.1513/pats.201001-008sm

Cited by 273 publications

(234 citation statements)

References 41 publications

(49 reference statements)

Supporting

Mentioning

211

Contrasting

Unclassified

Order By: Relevance

“…Inhalation of chlorine concentrations of 400 ppm or greater is generally fatal over 30 minutes. Asphyxia, respiratory failure, acute burns of the upper and lower airways, pulmonary edema, acute pulmonary hypertension, cardiomegaly, pulmonary vascular congestion, and death are some clinical features noted in victims after high-level chlorine exposures (1). Cardiomegaly was observed in autopsy of victims of acute chlorine poisoning in a major accidental cargo train derailment (2).…”

mentioning

confidence: 99%

Sarcoendoplasmic Reticulum Ca²⁺ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity

Ahmad

Hendry‐Hofer

et al. 2015

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Autopsy specimens from human victims or experimental animals that die due to acute chlorine gas exposure present features of cardiovascular pathology. We demonstrate acute chlorine inhalation-induced reduction in heart rate and oxygen saturation in rats. Chlorine inhalation elevated chlorine reactants, such as chlorotyrosine and chloramine, in blood plasma. Using heart tissue and primary cardiomyocytes, we demonstrated that acute highconcentration chlorine exposure in vivo (500 ppm for 30 min) caused decreased total ATP content and loss of sarcoendoplasmic reticulum calcium ATPase (SERCA) activity. Loss of SERCA activity was attributed to chlorination of tyrosine residues and oxidation of an important cysteine residue, cysteine-674, in SERCA, as demonstrated by immunoblots and mass spectrometry. Using cardiomyocytes, we found that chlorine-induced cell death and damage to SERCA could be decreased by thiocyanate, an important biological antioxidant, and by genetic SERCA2 overexpression. We also investigated a U.S. Food and Drug Administration-approved drug, ranolazine, used in treatment of cardiac diseases, and previously shown to stabilize SERCA in animal models of ischemia-reperfusion. Pretreatment with ranolazine or istaroxime, another SERCA activator, prevented chlorine-induced cardiomyocyte death. Further investigation of responsible mechanisms showed that ranolazine-and istaroximetreated cells preserved mitochondrial membrane potential and ATP after chlorine exposure. Thus, these studies demonstrate a novel critical target for chlorine in the heart and identify potentially useful therapies to mitigate toxicity of acute chlorine exposure. Clinical RelevanceThis study defines impact of inhalation of a toxic gas, chlorine, on a critical cardiac calcium pump, sarcoendoplasmic reticulum Ca 21 ATPase (SERCA). It also demonstrates that therapeutic strategies that protect or modify SERCA function could be useful approaches for emergent resuscitation of severe chlorine inhalation victims.Chlorine is a commonly used chemical in industry and society. Acute chlorine inhalation toxicity can occur due to accidents at swimming pools and/or involving water purification systems, after transportation accidents, upon industrial exposure, with misuse of domestic cleaners, during military operations, and, more recently, through chemical terrorism. In the

show abstract

mentioning

confidence: 99%

Sarcoendoplasmic Reticulum Ca²⁺ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity

Ahmad

Hendry‐Hofer

et al. 2015

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…Translational and animal studies demonstrate that acute chlorine-induced lung injury can produce precipitous functional decline, and the potential for irreversible epithelial damage (7)(8)(9)(10)(11). In humans, chlorine concentrations as low as 10 ppm can overcome upper airway defense mechanisms and penetrate into lower respiratory structures (12,13).…”

mentioning

confidence: 99%

Lung Function before and after a Large Chlorine Gas Release in Graniteville, South Carolina

et al. 2016

View full text Add to dashboard Cite

Rationale: On January 6, 2005 a train derailment led to an estimated 54,915-kg release of chlorine at a local textile mill in Graniteville, South Carolina.Objectives: We used the employee health spirometry records of the textile to identify enduring effects of chlorine gas exposure resulting from the incident on the lung function of workers employed at the textile mill.Methods: Spirometry records from 1,807 mill workers (7,332 observations) were used from 4 years before and 18 months after the disaster. Longitudinal analysis using marginal regression models produced annual population mean estimates for FEV 1 , FVC, and FEV 1 /FVC ratio. Covariate adjustment was made for sex, age, smoking, height, season tested, technician, obesity, season 3 year interactions, and smoker 3 year interactions. The increased prevalence of mill workers having accelerated FEV 1 decline was also evaluated after the chlorine spill. Measurements and Main Results:In the year of the accident, we observed a significant reduction in mean FEV 1 (-4.2% predicted; P = 0.019) when compared with the year before the incident. In the second year, partial recovery in the mean FVC % predicted level was seen, but the cohort's average FEV 1 /FVC ratio continued to decrease over time. Severe annual FEV 1 decline was most prevalent in the year of the accident, and independent of mill worker smoking status. Conclusions:The Graniteville mill worker cohort revealed significant reductions in lung function immediately after the chlorine incident. Improvement was seen in the second year; but the proportion of mill workers experiencing accelerated FEV 1 annual decline significantly increased in the 18 months after the chlorine incident.

show abstract

“…Administration of sodium bicarbonate produces a transient increase in sodium ion concentration, while its buffering action raises serum and urine pH. In medical toxicology practice, sodium bicarbonate is most commonly used in the treatment of tricyclic antidepressant (TCA) and salicylate poisoning; it is also effective as an adjuvant therapy for cocaine-induced ventricular dysrhythmias [2] and poisonings with quinine, chloroquine, and other type 1A and 1C antidysrhythmics [3]; methanol and ethylene glycol [4]; 2,4-dichlorophenoxyacetic acid and other chlorphenoxy herbicides [5,6]; and chlorine gas [7]. The rationale for sodium bicarbonate's therapeutic use varies by poisoning agent.…”

Section: Methodsmentioning

confidence: 99%

Sodium Acetate as a Replacement for Sodium Bicarbonate in Medical Toxicology: a Review

et al. 2013

View full text Add to dashboard Cite

Sodium bicarbonate is central to the treatment of many poisonings. When it was placed on the FDA drug shortage list in 2012, alternative treatment strategies to specific poisonings were considered. Many hospital pharmacies, poison centers, and medical toxicologists proposed sodium acetate as an adequate alternative, despite a paucity of data to support its use in medical toxicology. The intention of this review is to educate the clinician on the use of sodium acetate and to advise them on the potential adverse events when given in excess. We conducted a literature search focused on the pharmacology of sodium acetate, its use as a buffer in pathologic acidemia and dialysis baths, and potential adverse events associated with excess sodium acetate infusion. It appears safe to replace sodium bicarbonate infusion with sodium acetate on an equimolar basis. The metabolism of acetate, however, is more complex than bicarbonate. Future prospective studies will be needed to confirm the efficacy of sodium acetate in the treatment of the poisoned patient.

show abstract

Chlorine Gas Inhalation: Human Clinical Evidence of Toxicity and Experience in Animal Models

Cited by 273 publications

References 41 publications

Sarcoendoplasmic Reticulum Ca²⁺ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity

Sarcoendoplasmic Reticulum Ca²⁺ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity

Lung Function before and after a Large Chlorine Gas Release in Graniteville, South Carolina

Sodium Acetate as a Replacement for Sodium Bicarbonate in Medical Toxicology: a Review

Contact Info

Product

Resources

About

Chlorine Gas Inhalation: Human Clinical Evidence of Toxicity and Experience in Animal Models

Cited by 273 publications

References 41 publications

Sarcoendoplasmic Reticulum Ca2+ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity

Sarcoendoplasmic Reticulum Ca2+ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity

Lung Function before and after a Large Chlorine Gas Release in Graniteville, South Carolina

Sodium Acetate as a Replacement for Sodium Bicarbonate in Medical Toxicology: a Review

Contact Info

Product

Resources

About

Sarcoendoplasmic Reticulum Ca²⁺ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity

Sarcoendoplasmic Reticulum Ca²⁺ ATPase. A Critical Target in Chlorine Inhalation–Induced Cardiotoxicity