DERMAL TOXICITY of SULFUR MUSTARD

DERMAL TOXICITY of SULFUR MUSTARD Group 12: Tran Ngoc Trang Trinh Thi Thu Trang Vu Thi Thu Trang DERMAL TOXICITY of SULFUR MUSTARD A Introduction B Mechanism D Health Risk Assessment A Introduction I Background _ Chemical warfare agents (human-made) _Military use: extensively used during World War _Original name: LOST • SM (Sulfur mustard): bis(2-chloroethyl) is a simple chemical compound with the strong alkylating properties • Chemical structure: • Appearance: _Pure SM: colourless and odourless _In impure form (ex: warfare agents), SM is usually yellow-brown in colour • Barely soluble in water, but very soluble in fat, • Hazard: very toxic II Effects on skin _SM is “vesicant agent” _ Acute skin lesions : Blister (most prominent) Blister formation occurs at high doses: Vapour :1000-2000 mg min/m³ Liquid : 40 – 100 μg/cm² Blister on the legs of a Chinese soldier after exposure to SM gas 1941 Ulcer FIG: Deep ulcer after exposure to liquid SD Erythema Can frequently be observed 4-8h after skin contact at a threshold dose _ Vapour: 100 – 300 mg min/m³ _ Liquid : 10 – 20 μg/cm² _Long-term skin lesions: Skin xerosis (dry skin) pruritus, pigmentation disorders, scars Hyperpigmentation Frequently observed finding accompanying all SM skin lesions Example • Here is the onset of symptoms in 10 Iranian patients who were treated during 1984 and 1985 in hospitals in Munich, after exposure SM Time after exposure Wounds of Skin 10 1h Erythema 1/10 2h Erythema 1/10 4h Erythema 3/10; Blistering 3/10 6h Blistering 1/10 24h Blistering 1/10 No symptoms • Vesication started in 30% of the patients 4h after first SM contact • The typical signs and symptoms of cutaneous exposure to SM vapours were observed in all patients • To sum up: The process of SM induced skin pathology can be divided in three overlapping stages: erythematic, blister formation and ulceration They have been linked to variety of molecular mechanisms B Mechanism • 1st , SM is not very soluble in water but is very soluble in fat, contributing to its rapid absorption into the skin _In addition, percutaneous absorption depends on skin susceptibility _3 factors determining skin susceptibility to SM High temperature • 2nd , SM is a highly reactive chemical, which reacts with nearly all cell constituents • 3rd , DNA damage is believed to be the most critical lesion SM eliminates a chloride Cell Death/Tissue destruction (blister and ulcer) Development of Cancer Reaction of SM with N7 in Guanine _The most important reactions affect the DNA _The products are formed preferentially at the N7 position of guanine (67%) • However, SM not only reacts with cell constituents, mainly with DNA but also RNA, proteins and lipid membranes • Many cellular functions are disturbed as a consequence leading to cell death (apoptosis, necrosis), inflammation and impaired wound healing C Health Risk Assessment • At the threshold dose: _ Vapour: 100 – 300 mg min/m³ _Liquid : 10 – 20 μg/cm²  dermal symptoms occur 4-8h after exposure with itching and erythema • LD50 (skin) = 100 mg/kg • RfD for SM: 7x10⁻⁶ mg/kg/day • However, it should be kept in mind that Sulfur Mustard is a strong human carcinogen Conclusion • Sulfur Mustard is “vesicant agent” which is mainly used for military • Blistering, erythema and ulceration is the main skin damages They have been linked to variety of molecular mechanism • With the easy solubility in fat, SM is quickly absorbed into the skin • SM is a well-known carcinogen for human References (1) Acute effects of sulfur mustard injury – Munich experiences (2009 – K.Kehe) (2) Molecular toxicology of sulfur mustard-induced cutaneous inflammation and blistering (2008-K.Kehe) (3) Medical aspects of sulfur mustard poisoning (2005- Kai Kehe, Ladislaus Szinicz) (4) Dermal Toxicity of Sulfur Mustard (2009 –Donald R.Gerecke) [...]... well-known carcinogen for human References (1) Acute effects of sulfur mustard injury – Munich experiences (2009 – K.Kehe) (2) Molecular toxicology of sulfur mustard- induced cutaneous inflammation and blistering (2008-K.Kehe) (3) Medical aspects of sulfur mustard poisoning (2005- Kai Kehe, Ladislaus Szinicz) (4) Dermal Toxicity of Sulfur Mustard (2009 –Donald R.Gerecke) ... μg/cm²  dermal symptoms occur 4-8h after exposure with itching and erythema • LD50 (skin) = 100 mg/kg • RfD for SM: 7x10⁻⁶ mg/kg/day • However, it should be kept in mind that Sulfur Mustard is a strong human carcinogen Conclusion • Sulfur Mustard is “vesicant agent” which is mainly used for military • Blistering, erythema and ulceration is the main skin damages They have been linked to variety of molecular... believed to be the most critical lesion SM eliminates a chloride Cell Death/Tissue destruction (blister and ulcer) Development of Cancer Reaction of SM with N7 in Guanine _The most important reactions affect the DNA _The products are formed preferentially at the N7 position of guanine (67%) • However, SM not only reacts with cell constituents, mainly with DNA but also RNA, proteins and lipid membranes...• To sum up: The process of SM induced skin pathology can be divided in three overlapping stages: erythematic, blister formation and ulceration They have been linked to variety of molecular mechanisms B Mechanism • 1st , SM is not very soluble in water but is very soluble in fat, contributing to its