CARBON DISULFIDE ENCEPHALOPATHY

Pembimbing : Dr.Pukovisa Prawiroharjo, Sp.S

OLEH:

KELOMPOK 3

dr. Putriayu Hartini 1706080123

dr. Betharia Sonata 1806241596

dr. Adhi Pasha Dwitama 1806150673

dr. Ayu Munawaroh 1806150710

dr. Titil Sry Lestari 1806150805

dr. Kiki Rizkita 1806150761

 KATA PENGANTAR

Puji syukur kami panjatkan kehadirat Tuhan Yang Maha Esa, Makalah Carbon Disulfide
Encephalophaty dapat terselesaikan pada waktunya. Tugas yang disusun untuk memenuhi persyaratan
mata kuliah Penyakit Akibat Kerja di Progam Magister Kedokteran Kerja ini disusun berdasarkan referensi
dari berbagai sumber ilmiah.

Kami mengucapkan terima kasih kepada Dr. Pukovisa Prawiroharjo, Sp.S , selaku dosen pengajar
mata kuliah Penyakit Akibat Kerja. Tugas ini tentunya memiliki kekurangan baik berupa keterbatasan
referensi maupun teknik penulisan. Untuk itu, saran yang bersifat membangun sangat kami harapkan.

Jakarta, 19 Juni 2019

Penulis
 DAFTAR ISI

DAFTAR ISI..................................................................................................................................... i
KATA PENGANTAR ..................................................................................................................... ii
I. Characteristic Carbon Disulfide.....................................................................................................1
II.Biomechanism Carbon Disulfide....................................................................................................1

III.Route of Exposure.........................................................................................................................6

IV. Carbon Disulfide Exposure Effect.................................................................................................8

V.Pathophysiology Carbon Disulfide Encephalopathy.......................................................................9

VI.Cognitive Dysfunction due to Carbon Disulfide...........................................................................10

VII.Mental and Emotional Dysfunction due to Carbon Disulfide.....................................................11

VIII. Rehabilitation and Return to Work..........................................................................................13

IX. Prevention in Workplace............................................................................................................14

DAFTAR PUSTAKA .................................................................................................................... 17

 I. Characteristic of Carbon disulfide

Carbon dioxide is a physiologically important gas, produced by the body as a result of cellular
metabolism. It is widely used in the food industry in the carbonation of beverages, in fire
extinguishers as an 'inerting' agent and in the chemical industry. Carbon disulfide is an
organosulfur compound and a one-carbon compound. It is a clear colorless to light yellow volatile
liquid with a strong disagreeable odor. Boiling point 46° C. Flash point -22°F. Flammable over a
wide vapor/air concentration range(1%-50%). Vapors are readily ignited; the heat of a common
light bulb may suffice. Insoluble in water and more dense (10.5 lb / gal) than water. Hence sinks
in water. Vapors are heavier than air. Used in the manufacture of rayon and cellophane, in the
manufacture of flotation agents and as a solvent.

S=C=S

(Structure of carbon disulfide (CS2))

It is a counterirritant and has local anesthetic properties but is not used as such. It is highly toxic
with pronounced CNS, hematologic, and dermatologic effects. CS2 is highly flammable:

CS2 + 3 O2 → CO2 + 2 SO2

It is isoelectronic with carbon dioxide but it is more reactive toward nucleophiles and more easily
reduced. These differences in reactivity can be attributed to the weaker π donor-ability of the
sulfido centers, which renders the carbon more electrophilic.

II. Biomechanism of Carbon Disulfide

The metabolism of carbon disulfide is basically performed by two main pathways: Reaction with
amino acid and protein (glutathione) and via microsomal cytochrome p450 monooxigenase
system. Amino acid of blood react with carbon disulfide forming dithiocarbamic acid and cyclic
compound og the thiazolinone type. The free carbon disulfide present in the blood is distributed
to various tissues and organs, where it reacts with endorgenous amine to form acid labiles
metabolites (dithiocarbamates and 2-thio-5-thiazozolidinone) excreted in the urine.
Dithiocarbamatemetabolites are potensial chelating agents. A part of the carbondisulfide is
bound to gluthatione (GSH), forming thiazolidine-2-thione-4-carboxylic acid and then 2-
oxythiazolidine-4-carboxylic acid, ehich is excreted in urine.

The other metabolic pathway involves the microsomal cytochrome p450 monoxygenase system
catalyzing the oxidative desulfuration of carbon disulfide to an unstable oxygen intermediate.
The intermediate spontaneously degrades to atomic sulfur and carbonyl sulfide or undergoes
attack by wate, forming atomic sulfur and carbon dioxide. the atomic sulfur liberated in these
reactions can be covalently bound to the macromolecules or be oxidizes to sulfate and excreted
in urine. Formed carbonyl sulfide can be catalyzed by carbonic anhydrase to monothiocarbonate,
ehich is spontaneously degraded to carbon dioxide and HS. The HS is oxidizes to sulfate or other
still unknown metabolites. Monothiocarbonate can enter the urea cycle, forming thiourea, which
is excreted in urine.

The elimination of carbon dioxide via exhale air takes place in typical three phases process:
rapidly from respiration tract, more slowly from the blood, and very slowly from tissues and
organs. A small quantity of unchanged carbon disulfide is excreted via the urines, saliva, and
faeces. The excretion of free carbon disulfide through the skin is about three times greater than
that via the urine. The majority of metabolized carbon disulfide is excreted in the form of ethereal
sulfates and the other part in the form of the metabolites mention earlier.

On acute exposure, CS2 acts on the central nervous system (CNS) in humans and animals. In
humans, acute effects on the CNS following CS2 exposure manifest in dizziness, headaches,
autonomic nervous system reactions, nausea, vertigo, vomiting, central paralysis, and narcosis.
In animals (rats, mice, rabbits, cats, and dogs), acute exposure led to reduced activity but also
hyperexcitability, stupor, ataxia, tremors, convulsions, deep narcosis, and finally respiratory
arrest and death. Irritation of eyes and mucous membranes occur only at concentrations already
affecting the CNS. However, low concentrations without notable effects on the CNS led to an
inhibition of xenobiotic biotransformation reactions, inhibition of ethanol metabolism via the
alcohol and aldehyde dehydrogenase pathway, and alterations of carbohydrate and energy
metabolism in the liver.

In rats, 8 h of exposure to 20 ppm, the lowest concentration tested, also inhibited

biotransformation of drugs and solvents and caused a decrease of the glycogen content of the
liver. All effects were rapidly reversible within about 24 h, and no increase of liver enzymes in
serum was observed (Freundt and Dreher 1969; Freundt and Kuttner 1969; Kürzinger and
Freundt 1969; Freundt and Schauenburg 1971; Freundt et al. 1974b, 1976a; Freundt and
Kürzinger 1975). In one controlled human study, two volunteers were exposed to concentrations
from about 180 ppm to more than 3,000 ppm (Lehmann 1894).

III. Route of Exposures

1. Inhalation
Inhalation is the major route of exposure to carbon disulfide. The vapors are readily
absorbed by the lungs. The odor threshold is approximately 200 to 1,000 times lower than
the OSHA PEL-TWA (20ppm). Odors of pure or commercial grades of carbon disulfide
usually provide adequate warning of hazardous concentrations. Significant exposures to
carbon disulfide occur primarily in occupational settings. Acute exposure to carbon
disulfide vapors can be irritating to the eye, mucous membranes, and respiratory
epithelium. Acute exposure to concentrations that are orders of magnitude higher than
the OSHA exposure limit may cause severe neurological effects such as headache,
confusion, psychosis, coma, and even death. Being more than twice as heavy as air,
carbon disulfide vapors may be more concentrated in low-lying areas.

Children exposed to the same levels of carbon disulfide as adults may receive larger doses
because they have relatively greater lung surface area: body weight ratios and higher
minute volume: weight ratios. In addition, they may be exposed to higher levels than
adults in the same location because of their short stature and the higher levels of carbon
disulfide found nearer to the ground.
2. Skin/Eye Contact
Contact with liquid or concentrated vapors of carbon disulfide may cause irritation of the
skin, eyes, and mucous membranes. In extreme exposure cases, direct contact may cause
chemical burning of skin, eyes, or mucous membranes. Direct contact may result in
significant dermal absorption. Significant inhalation or dermal exposure to carbon
disulfide would most likely be encountered in an industrial environment, particularly
during rayon production. Because of their relatively larger surface area:weight ratio,
children are more vulnerable to toxicants absorbed through the skin.

3. Ingestion
Ingestion of carbon disulfide in amounts as small as 15 mL may result in the death of an
adult. Premortem symptoms include respiratory difficulty, tremors, convulsions, and
coma. Humans are unlikely to be exposed to significant quantities of carbon disulfide in
food or water.

Mechanisms of toxicity have not been clearly elucidated for carbon disulfide, but are thought
to be the result of the formation of carbon disulfide metabolites such as dithiocarbamates
and/or derivatives. Most absorbed carbon disulfide is rapidly metabolized; there appears to
be no substantial delay in the onset of adverse effects following acute exposure to high levels
of carbon disulfide. Direct contact with carbon disulfide results in local irritation, which may
be severe in cases of high-level exposure. Acute exposure to high concentrations of carbon
disulfide may result in rapid onset of both local irritation and concentration-dependent
increased severity of neurological symptoms such as nausea, dizziness, headache, delusions,
hallucinations, delerium, mania, psychosis, blurred vision, convulsions, and coma. Children
do not always respond to chemicals in the same way that adults do. Different protocols for
managing their care may be needed.
IV. Carbon Disulfide Exposure Effect

1. Cardiovascular
Chest pain and angina have been significantly related to acute carbon disulfide exposure
(Poisindex,2014)

2. CNS
Absorption of large amounts of carbon disulfide results in rapid onset of severe
neurological symptoms such as nausea, dizziness, headache, delusions, hallucinations,
delerium, mania, psychosis, blurred vision, convulsions, and coma. These symptoms are
dependent upon both exposure concentration and duration and may occur following
inhalation, oral, or dermal exposure. Death has been reported from exposure to a vapor
concentration of 4,815 ppm for 30 minutes. An exposure of 500 ppm for 30 minutes may
cause a situation immediately dangerous to life and health. Death due to carbon disulfide
poisoning may occur, in part, as a result of respiratory paralysis.

3. Respiratory
Acute exposure to carbon disulfide vapor concentrations of several hundred parts per
million may result in irritation of the upper respiratory tract. Children may be more
vulnerable to gas exposure because of higher minute ventilation per kg and failure to
evacuate an area promptly when exposed.

4. Ocular/Ophthalmic
Conjunctivitis and corneal burns can result from the irritant effect of carbon disulfide
vapor and from direct exposure to the liquid. Degenerative changes of the retina and optic
nerve may also result from acute exposure.

5. Dermal
Carbon disulfide is a skin irritant that causes pain, redness, and blisters, especially on
 mucous membranes. Carbon disulfide dissolves fatty layers of the epidermis. Therefore,
second and third degree chemical burns may result from direct contact during high-level
exposure. Because of their relatively larger surface area:body weight ratio, children are
more vulnerable to toxicants that affect the skin.

6. Gastrointestinal
Nausea, vomiting, and abdominal pain have been reported after acute exposure to carbon
disulfide.

7. Chronic Exposure
Chronic exposure to carbon disulfide can result in neurological effects similar to those
experienced during acute exposure, but at much lower exposure levels. In addition,
chronic exposure may cause effects such as permanent central and peripheral nervous
system damage, atherosclerotic tendencies, ECG abnormalities, gastrointestinal
disturbances, fatty degeneration of the liver, kidney damage, sexual dysfunction, hearing
loss, visual disturbances, retinal microaneurism, and blood dyscrasia. Chronic exposure
may be more serious for children because of their potential for a longer latency period.

8. Carcinogenicity
A carcinogenicity classification for carbon disulfide has not been established by the
Department of Health and Human Services, the International Association for Research on
Cancer, or the U.S. EPA.

V. Patophysiology CS2 Encephalopathy

The pathogenetic mechanisms of CS2 encephalopathy remain unclear. In some animal

studies, exposure to CS2 may induce distal axonopathy, particularly in the long, large-
diameter myelinated axons in the central and peripheral nervous systems
(Grahametal.,1995;Sillsetal.,2000;SpencerandSchaumburg, 1977). However, an increased
 incidence of coronary artery disease, retinopathy with macroaneurysm, and hyperlipidemia
was also found in CS2 intoxication (Hernberg et al., 1970, 1976; Luo et al., 2003; Oliver and
Weber, 1984; Sweetnam et al., 1987; Tiller et al., 1968; Tolonen, 1975). Vasculopathy has
been proposed in experimental studies (Lewey, 1941; Tolonen, 1975). In addition, a
disturbance of the focal cerebral blood flow was suggested, using brain single photon
emission computed tomography (SPECT) with xenon-133 studies (Aaserud et al., 1992). In a
previous study, we reported a small vessel disease in four patients with acute stroke-like
episodes due to CS2 intoxication (Huang et al., 2001). In order to understand the vascular
mechanisms of CS2 encephalopathy, we recruited four other patients with CS2 induced
encephalopathy, and used brain computed tomography(CT) perfusion scans and CT
angiography to evaluate them.

On computed tomography central nervous system lesions usually involve the basal ganglia
and subcortical white matter. Some authors reported that these cerebral lesions may
progress even after cessation of CS2 exposure (Huang et al., 1996; 2002, Aaserud et al., 1988,
1990). CS2-induced damage to peripheral nerves causes a distal axonal neuropathy that
seems to persist even after CS2 exposure had ceased for 3 years. In addition, a dose–
response relationship between CS2 exposure levels and the prevalence of PNP has been
found (Vanhoorne et al., 1995; Corsi et al., 1983).

VI. Cognitive dysfunction (brain fog)

Cognitive dysfunction is the loss of intellectual functions such as thinking, remembering, and
reasoning of sufficient severity to interfere with daily functioning. Patients with cognitive
dysfunction have trouble with verbal recall, basic arithmetic, and concentration.1

Long-term CS2 especially in low dose exposure, the symptoms, such as polyneuropathy,
parkinsonism with cogwheel rigidity, bradykinesia, and resting tremor, cerebellar ataxia, and
pyramidal tract symptoms may appear. In most patients, onset of CNS manifestation is
insidious and slowly progressive. For the subacute exposure, clinical features included
 nightmares, insomnia, mood fluctuatuion, excessive sexual behavior, paranoia, and slurred
speech. Following tremor, incoordination, ataxia, and memory impairment.1,2

Brain CT showed low density lesions in the basal ganglia and subcortical white matter,
indicating possible cerebral infarctions. Brain MRI revealed multiple high-signal intensity
lesions in the basal ganglia and subcortical white matter on T2-weighted images. Through the
brain CT perfusion, it showed diffuse decrease of regional blood flow and prolonged regional
mean transit time in the subcortical white matter.2

VII. Mental Emotional Dysfunction Due To Carbon Disulfide

Numerous epidemiological studies on carbon disulfide exposure among workers in viscose

rayon plants have been reviewed. Acute and subacute poisoning appear due to exposure to

carbon disulfide concentrations of 500-3000 mg/m3 and are characterized by

predominantly neurological and psychiatric symptoms, “encephalopathia sulfocarbonica”
such as irritability, anger, mood changes, manic delirium and hallucinations, paranoic ideas,
loss of appetite, gastrointestinal disturbances and sexual disorders.

More subtle neurological changes at lower carbon disulfide concentrations have been
reported; the symptoms are a reduction of nerve conduction velocities and psychological
disturbances. In workers exposed for 10-15 years to carbon disulfide in concentrations of

around 10 mg/m3, sensory polyneuritis and increased pain threshold were reported. These
neurological disturbances were accompanied by psychological and neurobehavioural
disorders.

M philip et all 1993 have done research to determine the concentrations of pentane (a
marker of lipid peroxidation) and other volatile organic compounds in the breath of patients
with schizophrenia. Volatile organic compounds were assayed by gas chromatography/mass
spectroscopy (GCIMS) in 88 subjects-25 with acute schizophrenic psychosis, 26 with
psychiatric disorders other than schizophrenia, and 37 normal volunteers. The mean
alveolar gradients of pentane and carbon disulfide (CS2) were significantly higher in the
patients with schizophrenia than in the control groups. Schizophrenia may be accompanied
by accelerated lipid peroxidation in cell membranes, as well as increased manufacture of
CS2, a known neurotoxin.

Dysfunctions in the central nervous system are wellknown manifestations of adverse CS2
effects. Developed psychiatric signs and symptoms are rare as aresult of changes in
technology and improved working conditions, Instead, tiredness, sleepiness, affectlability,
irritability, memory disturbances, decrease in intellectual capacity, as well as dizziness,
headache andreduction in libido, are reported. Psychological tests inworkers exposed to
long-term low levels of CS2 have revealed different neurobehavioral changes, such asvisual-
perceptive, psychomotor or cognitive changes. Despite progress in understanding the
neurotoxicity of CS2 exposure, some problems still exist. First of all,different terms are used
for similar disorders, such astoxic encephalopathy, psychoorganic syndrome,dementia,
neurobehavioral effects, chronic solvent syndrome .The development of neuropsychiatric
symptoms due to high CS2 levels, mostly in viscose rayon factories inJapan and Italy, were
described in the 1960s and1970s. An investigation in a viscose rayon plant in Norway, where
concentrations of CS2 were below 30 mg/m3 but with peak exposures of CS2, showed that
4 yr after the cessation of exposure in 14 out of 16 workers toxic encephalopathy was
diagnosed. Most frequent symptoms were memory impairment, irritability,tiredness, and
sleep disorders

Srmena Krstev, 2003 has done research on prevalence of dysfunctions of the central nervous
system wasassessed in 134 male workers exposed to differen tlevels of carbon disulfide
(CS2) in a rayon viscose plantand compared to 38 non-exposed workers. In three groups of
workers from the same plant with different levels of CS2 (heavy, intermediate, none)
estimated bypersonal samplers, disorders in the central nervous system were examined by
means of psychiatric examination and questionnaire 16 (Q16). High correlation was found
between symptom recorded on neuropsychiatric examination and on Q16. Both
neuropsychiatric exams and Q16 indicated disturbances in the central nervous system due
 to the long-term heavy exposure to CS2. Disorders of the central nervous system were
found more often inworkers with heavy exposure to CS2. Questionnaire Q16 is a valuable
means for selecting workers for further neuropsychiatric testing.

VIII. Rehabilitation and Return To Work

Return to work management involves many parties/disciplines. This programme gets people
back to work in order to make them better (do not make people better in order to get them
back to work). This programme is very important for company and worker to place the
worker fit to the job after workplace injury/work related disease. There are many impacts of
time off work due to work place injury to worker or employer. Impact on injured worker for
examples are financial and emotional stress, loss of confidence and self-esteem, loss of social
networks, dependence on disability payments or unemployment benefits. Impact to
employer for examples are increased worker’s compensation premium, reduced
productivity, increased recruitment/training cost, a drop in staff morale, etc.

Now Indonesia has policy and regulation and potential resources regarding the return to
work programme. Act No. 13 - 2003 concerning labour, act 29- 2004 concerning medical
practices, act no 40 -2004 concerning national social security system, government decree
no. 44- 2005 concerning the procedures of occupational accident benefit and death benefit,
ministry of labour decree no. 10 – 2016 concerning of return to work programme and
promotive and preventive activities of occupational diseases.

The RTW (return to work) programme attempt to address the reducing high rates of sickness
absence and poor levels of return to work following absence. The responsible institution for
providing RTW programme in Indonesia is the BPJS Ketenagakerjaan by providing health
services, rehabilitation and cases training.

The basic principle of RTW programme are: (skivington, 2016)

 Organizational commitment
  Creating return to work plan
 Support returning worker without disadvantaging co-workers
 Supervisors are trained in the work disability prevention an included in RTW
planning
 Early contact with the worker
 Responsible RTW coordinator
 Employers and health care providers communicate each other about the
workplace need.

The aim of RTW programme is to ensure the post injured/sick worker able to do the duty
effectively and safely for the worker and the other.In assessing the RTW, we need to know
details of the job descriptions, the job demand, current medical status, impairment, and
risk for the worker and co-worker, adjustment to fit with the same job/other job.

IX. Prevention In Worplace

Control of exposure to gas and vapour, alongside other health and safety measures and
environmental protection, should be a key priority of the top level management, and
workers should continually be made aware that this is a management priority. Incentive
systems for supervisors and workers should be designed to encourage safe procedures
and not just productivity.

Prevention and control measures should be integrated into comprehensive, well-

managed and sustainable programmes at the workplace level, involving management,
workers, production and occupational health professionals.

There are 5 hierarchy of controls:

1. Elimination

CS2 substance may be eliminated by changing the process so that the substance is no
longer needed.
2. Substitution
If elimination is not feasible, try to use a less hazardous substance as a substitute. It is,
of course, necessary to assess all of the effects of the change. It will be necessary to
assess and control any eventual new risks.

3. Engineering Controls
If substitution is not feasible, ways should be engineering controls with containment
and ventilation.

Containment consists in placing a physical barrier between the CS2 substance and
people, for example putting a process inside a box. It may be satisfactory to partially
enclose a process, for example, by having an opening at the front of an enclosure for
the operator to reach in (however, the worker’s breathing zone should never be
between the contaminant source and the hood). Effective design is difficult, because
the flow of air into the opening must be sufficient to prevent escape of the airborne
material, including when people move across the opening.

Local exhaust ventilation is the removal of airborne contaminants, close to their source
of generation or release, before they can spread and reach the worker’s breathing
zone. For this, it is necessary to ensure that the airflow is sufficient and its direction
appropriate.

General ventilation is usually desirable to control the temperature and humidity of the
environment, and a properly designed system can act as a back-up control of exposure
to airborne substances, by providing continual dilution of any accidental emissions.
General ventilation can be used to control widely disseminated low toxicity of CS2.
 Ventilation must be so designed that movements of personnel and vehicles, or the
opening of doors and windows, cannot jeopardize its effectiveness. The design of
ventilation systems should always be the responsibility of specially trained
professionals.

It is essential that managers ensure a continued and effective inspection and

maintenance programme, so that ventilation systems continue to work as designed,
and that workers are properly informed and trained about their use.

It is necessary to ensure that ventilation does not move contaminated air to

unsuspecting workers downstream, and that hazardous substances are not exhausted
to the general environment in an unplanned and undesirable way. When dealing with
toxic contaminants, air cleaning devices must be incorporated in ventilation systems,
in order to prevent their discharge to the outside environment, and also to prevent re-
circulation to the workplace.
4. Administrative Controls
The manner in which a worker performs a task can appreciably affect exposure, so it
is important to train workers in good work practices. Video recording of tasks, with
simultaneous measurement of airborne concentrations, can be a useful tool for
designing and training in adequate work practices.

Personal care, including teeth brushing, washing hands and cleaning nails, showering
and washing hair, before eating and after the work are important measures whenever
there is the possibility of dust contamination. Workers must be properly trained about
the hazards and risks from the substances used, the control measures, and any
exposure monitoring. The workers are often the people who have the fullest
knowledge of what happens during work, and their views should be sought on what
leads to exposure and the effectiveness of control.
5. Personal Protective Equipment (PPE)
Every attempt should be made to avoid or minimize exposure by other methods before
resorting to personal protective equipment (PPE), especially respiratory protective
equipment (RPE). A respirator, particularly of the mask type, is not easy to wear for
long periods; it can be very uncomfortable, especially in hot or cramped conditions,
and workers may be tempted to remove it. Another problem is that PPE is fallible, and
may not give the protection assumed; moreover, it offers no environmental
protection. Finally, PPE and especially RPE must be conscientiously cleaned and
maintained to remain effective, which often makes them a costly option; poor
maintenance makes any PPE ineffective. Areas where there is a need for the use of
PPE or other precautions should be clearly indicated by warning signs.
 DAFTAR PUSTAKA

1. Aaserud O, Hommeren OJ, Tvedt B, et al. Carbon disulfide exposure and neurotoxic
sequelae among viscose rayon workers. Am J Int Med 1990;18:25-37.
2. Huang CC. Carbon Disulfide Neurotoxicity: Taiwan Experience. Acta neurologica
taiwanica. Vol 13(1); 2004.
3. Wen-Li Chuang a, Chin-Chang Huang a, Chi-Jen Chen b, Yu-Chen Hsieh a, Hung-Chou Kuo
a, Tung-Sheng Shih. Carbon disulfide encephalopathy: Cerebral
microangiopathyDepartment of Neurology, Chang Gung Memorial Hospital and
University, Taipei, Taiwan. 2006.
4. Lode Godderisa, Lutgard Braeckmanb, Michel Vanhoorneb, Mineke Viaenea,c.
Neurobehavioral and clinical effects in workers exposed to CS2. Department of
Occupational, Insurance and Environmental Medicine, Catholic University of Leuven,
Belgium b Department of Public Health, Section of Occupational and Environmental
Medicine, Ghent University, Belgium. September 2005