Model for assessing efficacy of topical skin protectants against sulfur mustard vapor using hairless guinea pigs.

Published on Dec 1, 1999in Journal of Applied Toxicology2.997
· DOI :10.1002/(SICI)1099-1263(199912)19:1+<S55::AID-JAT616>3.0.CO;2-W
Thomas H. Snider6
Estimated H-index: 6
(Battelle Memorial Institute),
M. C. Matthews2
Estimated H-index: 2
(Battelle Memorial Institute),
Ernest H. Braue12
Estimated H-index: 12
(DA: United States Department of the Army)
Source
Abstract
: 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 of HGPs were exposed percutaneously for various lengths of time to HD vapor. In one set, the HGPs were sacrificed 24 h after exposure, and skin specimens were collected and processed for histopathology. In the other set, light reflectance was measured at skin test sites 4, 5, 6 and 24 h after exposure, to assess erythema. The Nikolsky's sign test was also performed 24 h after exposure by rotating a metal disk glued to the skin test site and inspecting the skin for loss of epidermis. Probit analysis of data indicated that the exposure durations that produced a 50% incidence of microblisters and Nikolsky's sign were ca. 7.5 and 4.5 min, respectively. Maximum erythema was observed 6 h following a 6 min exposure. Operating parameters for assessing the efficacies of skin protectants have been characterized.
📖 Papers frequently viewed together
86 Citations
65 Citations
25 Citations
References0
Newest
Cited By10
Newest
#1Laurie B. Joseph (RU: Rutgers University)H-Index: 12
#2Diane E. Heck (NYMC: New York Medical College)H-Index: 38
Last. Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
view all 10 authors...
Abstract Sulfur mustard (SM) is a bifunctional alkylating agent causing skin inflammation, edema and blistering. A hallmark of SM-induced toxicity is follicular and interfollicular epithelial damage. In the present studies we determined if SM-induced structural alterations in hair follicles and sebaceous glands were correlated with cell damage, inflammation and wound healing. The dorsal skin of hairless mice was treated with saturated SM vapor. One to seven days later, epithelial cell karyolysis...
10 CitationsSource
#1Hassan GhasemiH-Index: 15
#2Parviz OwliaH-Index: 26
Last. Tooba GhazanfariH-Index: 21
view all 18 authors...
AbstractContext: Sulfur mustard (SM), with an old manufacturing history still remains as potential threat due to easy production and extensive effects.Objectives: Increasing studies on SM indicates the interest of researchers to this subject. Almost all human body organs are at risk for complications of SM. This study offers organ-by-organ information on the effects of SM in animals and humans.Methods: The data sources were literature reviews since 1919 as well as our studies during the Iraq–Ira...
21 CitationsSource
#1Shlomit Dachir (Israel Institute for Biological Research)H-Index: 19
#2Maayan Cohen (Israel Institute for Biological Research)H-Index: 10
Last. Tamar Kadar (Israel Institute for Biological Research)H-Index: 26
view all 9 authors...
Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measuremen...
9 CitationsSource
#1Virginie ValletH-Index: 1
#2T. Poyot (AG: Analysis Group)H-Index: 1
Last. Isabelle BoudryH-Index: 9
view all 7 authors...
Sulfur mustard (HD) ranks among the alkylating chemical warfare agents. Skin contact with HD produces an inflammatory response that evolves into separation at the epidermal–dermal junction conducting to blistering and epidermis necrosis. Up to now, current treatment strategies of HD burns have solely consisted in symptomatic management of skin damage. Therapeutic efficacy studies are still being conducted; classically using appropriate animal skin toxicity models. In order to substantiate the us...
13 CitationsSource
#1Janet M. Benson (LRRI: Lovelace Respiratory Research Institute)H-Index: 30
#2Brad M. Tibbetts (LRRI: Lovelace Respiratory Research Institute)H-Index: 5
Last. Gary R. Grotendorst (LRRI: Lovelace Respiratory Research Institute)H-Index: 32
view all 4 authors...
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 tran...
9 CitationsSource
#1Janet M. Benson (LRRI: Lovelace Respiratory Research Institute)H-Index: 30
#2JeanClare Seagrave (LRRI: Lovelace Respiratory Research Institute)H-Index: 31
Last. Thomas H. March (LRRI: Lovelace Respiratory Research Institute)H-Index: 22
view all 7 authors...
The objective of these studies was to provide detailed analyses of the time course of sulfur mustard (SM) vapor-induced clinical, histological, and biochemical changes following cutaneous exposure in hairless guinea-pigs. Three 6 cm2 sites on the backs of each guinea-pig were exposed to SM vapor (314 mg3) for 6 minutes (low dose) or 12 minutes (high dose). Animals were killed at 6, 24, and 48 hours, or 2 weeks postexposure. Erythema, edema, histopathology, and analysis of matrix metalloproteinas...
22 CitationsSource
#1Shlomit Dachir (Israel Institute for Biological Research)H-Index: 19
#2Maayan Cohen (Israel Institute for Biological Research)H-Index: 10
Last. Tamar Kadar (Israel Institute for Biological Research)H-Index: 26
view all 7 authors...
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...
25 CitationsSource
#1G. KarvalyH-Index: 4
#2A. GachályiH-Index: 1
Last. J. FürészH-Index: 1
view all 3 authors...
Subcutaneous microdialysis was employed for monitoring thiodiglycol (2,2′-thiodiethanol, TDG) levels with the aim of characterizing the transdermal penetration of topically applied liquid sulfur mustard (2,2′-dichlorodiethyl sulfide, SM) in rats. TDG levels, evaluated in 20 min dialysates collected over a 6 h sampling period, were plotted against time after pooling. Linear correlation was identified between the SM dose and the mean areas under the 0–60 min or the whole curve (AUC0–60 and AUC, re...
4 CitationsSource
#1John S. GrahamH-Index: 18
#2Robert P. ChilcottH-Index: 23
Last. Beverly I MalinerH-Index: 1
view all 6 authors...
Sulfur mustard is an alkylating chemical warfare agent that primarily affects the eyes, skin, and airways. Sulfur mustard injuries can take several months to heal, necessitate lengthy hospitalizations, and result in significant cosmetic and/or functional deficits. Historically, blister aspiration and/or deroofing (epidermal removal), physical debridement, irrigation, topical antibiotics, and sterile dressings have been the main courses of action in the medical management of cutaneous sulfur must...
75 Citations
#1Dana R. Anderson (United States Army Medical Research Institute of Chemical Defense)H-Index: 25
#2Larry W. Mitcheltree (United States Army Medical Research Institute of Chemical Defense)H-Index: 4
Last. Mark B. Gold (United States Army Medical Research Institute of Chemical Defense)H-Index: 4
view all 6 authors...
Sulfur mustard (HD) is a vesicant compound that was first used as a chemical warfare agent in World War I. (Papirmeister et al. 1991). Numerous animal models have been used to study HD-induced vesication. In this article, we describe modifications of the vapor cup model of Mershon and colleagues (1990) to establish a new vapor cup model for use in neonatal mice. The need to develop this model resulted from the development of gene-targeted knockout mice that can be used to evaluate the function o...
4 CitationsSource