Rapid Assessment of Exposure to Chlorine Released from a Train Derailment and Resulting Health Impact

Wenck, Mary Anne; Sickle, David Van; Drociuk, Daniel; Belflower, Amy; Youngblood, Claire; Whisnant, M. David; Taylor, Richard W.; Rudnick, Veleta; Gibson, James J.

doi:10.1177/003335490712200610

Cited by 58 publications

(74 citation statements)

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“…Besides pulmonary edema and respiratory failure, more than 90% of fatalities due to acute high-level chlorine exposure may be due to cardiovascular complications (1,(22)(23)(24). Our earlier studies with environmental oxidant gas exposures revealed enhanced airway epithelial cell death and subsequent loss of SERCA activity (17,25).…”

Section: Discussionmentioning

confidence: 91%

“…These studies proposed a role for particulate matter-induced cardiovascular inflammation and oxidative stress (29). Cardiac effects of chlorine, especially cardiomegaly, were reported in autopsies of human victims of acute high-concentration chlorine gas exposure (1,(22)(23)(24). Similarly, experimental dogs that died of acute chlorine exposure had dilated right ventricles (30).…”

Section: Discussionmentioning

confidence: 99%

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

Ahmad

Hendry‐Hofer

et al. 2015

Am J Respir Cell Mol Biol

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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

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

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

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“…We believed that employee annual spirometry assessments could be used to assess community lung health before and after the train accident. Mill buildings were located in close proximity to the crash site, and nearly 200 employees were working at the time of the accident (4). Moreover, the accident occurred at 02:40 hours, and many mill worker residents were exposed to chlorine while sleeping in their nearby homes.…”

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confidence: 99%

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

et al. 2016

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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.

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“…Cl 2 gas exposure is a documented public health threat mainly because of accidents involved in its trafficking and deliberate release involved in warfare; therefore increased preparedness is required to avoid mass casualty situations (26,51,55,56). Apart from the fact that significant morbidity and mortality are entailed in cases of acute exposure, there are also long-term residual clinical symptoms, such as reactive airway disease syndrome, reduced residual volume, and reduced forced vital capacity (4,12,16,45).…”

Section: Discussionmentioning

confidence: 99%

Postexposure aerosolized heparin reduces lung injury in chlorine-exposed mice

Zarogiannis

Wagener

Basappa

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Rapid Assessment of Exposure to Chlorine Released from a Train Derailment and Resulting Health Impact

Cited by 58 publications

References 1 publication

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

Postexposure aerosolized heparin reduces lung injury in chlorine-exposed mice

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Rapid Assessment of Exposure to Chlorine Released from a Train Derailment and Resulting Health Impact

Cited by 58 publications

References 1 publication

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

Postexposure aerosolized heparin reduces lung injury in chlorine-exposed mice

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

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