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 min
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)