Uptake, Tissue Distribution, and Excretion of 14C-Sulfur Mustard Vapor Following Inhalation in F344 Rats and Cutaneous Exposure in Hairless Guinea Pigs

Published on May 18, 2011in Journal of Toxicology and Environmental Health2.653
· DOI :10.1080/15287394.2011.567959
Janet M. Benson29
Estimated H-index: 29
(LRRI: Lovelace Respiratory Research Institute),
Brad M. Tibbetts5
Estimated H-index: 5
(LRRI: Lovelace Respiratory Research Institute)
+ 1 AuthorsGary R. Grotendorst32
Estimated H-index: 32
(LRRI: Lovelace Respiratory Research Institute)
Sources
Abstract
Sulfur mustard (SM), a vessicating agent, has been used in chemical warfare since 1918. The purpose of this study was to quantitate SM vapor deposition, tissue distribution, and excretion following intratracheal inhalation in rats and cutaneous exposure in guinea pigs. 14C-SM vapors for inhalation studies were generated by metering liquid 14C-SM into a heated J tube. Vapors were transported via carrier air supplemented with oxygen and isoflurane to an exposure plenum. Anesthetized rats with transorally placed tracheal catheters were connected to the plenum port via the catheter hub for exposure (approximately 250 mg 14C-SM vapor/m3; 10 min). For dermal exposure, 3 Teflon cups (6.6 cm2 exposure area per cup) were applied to the backs of each animal and vapors (525 mg 14C-SM/m3; 12 min) were generated by applying 6 μl 14C-SM to filter paper within each cup. Animals were euthanized at selected times up to 7 d postexposure. SM equivalents deposited in rats and guinea pigs were 18.1 ± 3 μg and 29.8 ± 5.31 μg, ...
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References18
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#1Waylon Weber (LRRI: Lovelace Respiratory Research Institute)H-Index: 13
#2Dean Kracko (LRRI: Lovelace Respiratory Research Institute)H-Index: 12
Last. Jacob D. McDonald (LRRI: Lovelace Respiratory Research Institute)H-Index: 45
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Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a l...
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#1Shlomit Dachir (Israel Institute for Biological Research)H-Index: 19
#2Maayan Cohen (Israel Institute for Biological Research)H-Index: 9
Last. Tamar Kadar (Israel Institute for Biological Research)H-Index: 26
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Background/purpose: Skin exposure to sulfur mustard (HD) results in erythema, edema and severe injury, which take long time to heal and might impose a heavy burden on the health system. Despite many years of research, there is no treatment that prevents the development of the cytotoxic effects of HD causing acute and prolonged damage to the skin. Therefore, it is of great importance to develop treatments that will ameliorate the extent of injury and improve as well as shorten the healing process...
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#1Neerad C. Mishra (LRRI: Lovelace Respiratory Research Institute)H-Index: 19
#2Jules Rir-sima-ah (LRRI: Lovelace Respiratory Research Institute)H-Index: 8
Last. Mohan L. Sopori (LRRI: Lovelace Respiratory Research Institute)H-Index: 28
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Sulfur mustard (SM, bis-(2-chloroethyl) sulfide) is a well known chemical warfare agent that may cause long-term debilitating injury. Because of the ease of production and storage, it has a strong potential for chemical terrorism; however, the mechanism by which SM causes chronic tissue damage is essentially unknown. SM is a potent protein alkylating agent, and we tested the possibility that SM modifies cellular antigens, leading to an immunological response to “altered self” and a potential lon...
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#1Monica Kathleen Wattana (UCI: University of California, Irvine)H-Index: 1
#2Tareg Bey (UCI: University of California, Irvine)H-Index: 13
Sulfur mustard is a member of the vesicant class of chemical warfare agents that causes blistering to the skin and mucous membranes. There is no specific antidote, and treatment consists of systematically alleviating symptoms. Historically, sulfur mustard was used extensively in inter-governmental conflicts within the trenches of Belgium and France during World War I and during the Iran-Iraq conflict. Longitudinal studies of exposed victims show that sulfur mustard causes long-term effects leadi...
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#1I. J. Hattersley (SU: Salisbury University)H-Index: 1
#2John Jenner (SU: Salisbury University)H-Index: 10
Last. John S. GrahamH-Index: 18
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Abstract Studies of the percutaneous reservoir of sulphur mustard (HD) formed during absorption carried out during WWI and WWII are inconclusive. More recent studies have indicated that a significant amount of unreacted HD remains in human epidermal membranes during percutaneous penetration studies in vitro. The present study investigated the nature and persistence of the HD reservoir formed during in vitro penetration studies using dermatomed slices of human and pig skin (0.5 mm thick). Amounts...
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#1Christopher H. Dalton (SU: Salisbury University)H-Index: 10
#2Michael P. Maidment (SU: Salisbury University)H-Index: 5
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Percutaneous vapor dosing studies have generally used saturated vapor concentration (SVC) measurements to estimate the exposure dose (Ct) of vapor produced from a volatile liquid within a closed system. The purpose of this study was to clarify whether the
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#1Uri Wormser (HUJI: Hebrew University of Jerusalem)H-Index: 20
#2Berta Brodsky (HUJI: Hebrew University of Jerusalem)H-Index: 15
Last. Amnon Sintov (BGU: Ben-Gurion University of the Negev)H-Index: 25
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Sulfur mustard (SM, mustard gas) is a chemical warfare vesicant that rapidly penetrates the skin due to its hydrophobicity. This study measured the rate of SM disappearance from the skin after topical application of the vesicant. In both fur-covered and hairless animals, the remaining toxicant levels measured 60 min after exposure to undiluted SM were 0.6% and 0.3%, respectively, of the initially applied SM amount. However, SM concentration reached 0.4% of the initial dose 3 h following exposure...
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#1H Sueki (UPenn: University of Pennsylvania)H-Index: 1
#2C GammalH-Index: 1
Last. A M KligmanH-Index: 1
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In order to characterize the microscopic anatomy of hairless guinea pig (HL-GP) skin, we utilized light microscopy with a computer-assisted image analysis system, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM revealed that the hair shafts of HL-GPs were thin, short, extremely irregular in diameter and often twisted and curled. The HL-GP epidermis was of similar thickness to that of human skin with distinct strata, serrated/non-serrated basal keratinocytes and...
#1Thomas H. Snider (Battelle Memorial Institute)H-Index: 7
#2M. C. Matthews (Battelle Memorial Institute)H-Index: 2
Last. Ernest H. Braue (DA: United States Department of the Army)H-Index: 12
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: Sulfur mustard (HD; 2,2'-dichlorodiethyl sulfide) can produce incapacitating blisters in humans following dermal exposure. Most non-human animal models, however, do not form the large fluid-filled blisters observed in humans. Many models, nevertheless, do produce similar damage at the dermal/epidermal junction when evaluated by histopathology. In this study, it was observed that the hairless guinea pig (HGP) exhibits similar histopathological responses following exposure to HD vapor. Two sets ...
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In order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard (SM) the toxicokinetics of this agent as well as its major DNA-adduct were studied in male hairless guinea pigs for the intravenous, respiratory and percutaneous routes. the study comprised measurement of the concentration-time course of SM in blood and measurement of the concentrations of intact SM and its adduct to guanine in various tissues at several time points after administration of,...
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Abstract Oxidative stress, DNA damage repair, and inflammation are three important reactions of sulfur mustard (SM) exposure. But molecular related chronological events in the earlier stage of SM exposure model are still unclear. In the research, reactive oxygen species (ROS) was measured by using flow cytometry. Cytokines were tested in Luminex method. Myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG) and glutathione (GSH) activity or levels in s...
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Nitrogen mustard (NM) is a vesicant that causes lung injury and fibrosis, accompanied by a persistent macrophage inflammatory response. In these studies we analyzed the spleen as a source of these cells. Splenectomized (SPX) and sham control rats were treated intratracheally with NM (0.125 mg/kg) or PBS control. Macrophage responses were analyzed 1–7 days later. Splenectomy resulted in an increase in lung macrophages expressing CCR2, but a decrease in ATR-1α+ cells, receptors important in bone m...
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4 ACKNOWLEDGEMENTS 5 CONTENTS 6 LIST OF ORIGINAL PUBLICATIONS 8 GENERAL ABBREVIATIONS 9 ABBREVIATIONS OF CHEMICALS 11
#1Adel Ghorani-Azam (MUMS: Mashhad University of Medical Sciences)H-Index: 9
#2Mahdi Balali-Mood (MUMS: Mashhad University of Medical Sciences)H-Index: 25
Sulfur mustard (SM) and nitrogen mustard (NM) are the two types of mustard compounds (MCs). SM has mainly been used as a chemical warfare agent (CWA), but NM has been administered as an anti-cancer drug. MCs are alkylating agents and initially synthesised for military purposes as a chemical blistering agent. However, they were also used as medications in the treatment of several diseases such as psoriasis and variety of cancers. MCs, especially SM can cause acute and chronic toxicities, particul...
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#1Harald JohnH-Index: 27
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Nerve agents and vesicants still represent important chemical warfare agents (CWAs) threatening military and civilian communities, most likely by means of terrorist attacks and asymmetric warfare. Therefore, nations should be prepared to both protect their people and cure them after poisoning by the most appropriate therapy and efficient antidotes. The latter purpose requires an in-depth understanding of interactions between the toxicant, compartments, and biomolecules of an organism highly rele...
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#1Miroslav Pohanka (University of Defence)H-Index: 33
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Sulfur mustard (SM) is a chemical warfare agent with cytotoxic effect and a tight link to oxidative stress (OS). Depletion of antioxidants is considered as a cause of detrimental consequence and belongs to the important steps leading to cell death. The oxidative injury appearing after SM exposure is not well understood. Nevertheless, identification of the pathological processes would be a good opportunity to establish an efficient therapy. Here, we focused our effort on an estimation of reactive...
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#1Camilla Della Torre (UNISI: University of Siena)H-Index: 20
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Abstract The aim of this study was to evaluate the potential toxicological effects on fish related to the leakage of yperite from rusted bomb shells dumped at sea. Both in vivo and field studies have been performed. As for the in vivo experiment, specimen of European eel were subcutaneously injected with 0.015, 0.15 and 1.5 mg/kg of yperite and sacrificed after 24 and 48 h. In the field study, specimen of Conger eel were collected from a dumping site in the Southern Adriatic Sea. The presence/ab...
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#1Robin M. Black (SU: Salisbury University)H-Index: 27
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In cases of investigations into alleged use of chemical warfare agents, biomedical samples such as urine or blood may be collected from casualties for forensic analysis. Analysis of biomedical samples may also be undertaken for diagnostic purposes, to ensure appropriate medical treatment, and for occupational exposure monitoring, e.g. in workers engaged in demilitarization activities. Metabolites excreted in urine, or circulating in the blood, provide unequivocal biological markers of exposure. ...
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#1Waylon Weber (LRRI: Lovelace Respiratory Research Institute)H-Index: 13
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Sulfur mustard (SM) is a chemical threat agent for which the effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present article details the techniques used to develop SM laboratory exposure systems for the development of animal models of ocular and dermal injury. These models are critical to enable evaluation of SM injury and therapeutics against that injury. Iterative trials were conducted to optimize ...
Source
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