UKPID MONOGRAPH
ANTIMONY POTASSIUM TARTRATE
WN Harrison PhD CChem MRSC
SM Bradberry BSc MB MRCP
JA Vale MD FRCP FRCPE FRCPG FFOM
National Poisons Information Service
(Birmingham Centre),
West Midlands Poisons Unit,
City Hospital NHS Trust,
Dudley Road,
Birmingham
B18 7QH
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
ANTIMONY POTASSIUM TARTRATE
Toxbase summary
Type of product
Industrial chemical and pesticide. Has been used as an anti-parasitic
drug.
Toxicity
The most toxic trivalent antimony compound. A potent emetic. Ingestion
of 0.2 g has been reported to be fatal (Miller, 1982) although a child
has survived the ingestion of 2.3 g (Iffland and Bosche, 1987).
Features
Topical
- Irritant to the skin and eyes.
- "Antimony spots" (papules and pustules around sweat and
sebaceous glands) may develop after repeated exposure,
particularly in warm conditions.
Inhalation
- Irritant to the respiratory tract and mucous membranes
causing conjunctivitis, laryngitis, pharyngitis, tracheitis,
rhinitis bronchitis and rarely non-cardiogenic pulmonary
oedema.
- There may be radiological evidence of pneumonitis.
- Chronic occupational inhalation may cause pneumoconiosis
with cough, wheeze and diffuse, punctate opacities in the
middle and lower zones.
Ingestion
Moderate ingestions:
- Features usually start within 30 minutes to two hours with
nausea, vomiting, abdominal pain and diarrhoea. A garlic
odour on the breath has been described following ingestion
of antimony salts.
Substantial ingestions:
- Severe vomiting and diarrhoea (which may contain blood) and
haemorrhagic gastritis may ensue. Myocardial depression,
vasodilation and fluid loss may cause shock with
hypotension, electrolyte disturbances and acute renal
failure. Cerebral oedema, coma and convulsions are possible.
Fatalities have occurred (Miller, 1982).
Injection
- The treatment of leishmaniasis and schistosomiasis has been
associated with anorexia, nausea, vomiting, abdominal pain,
a metallic taste, diarrhoea, pancreatitis, reversible
elevation of liver enzyme activities, myalgia, arthralgia,
proteinuria, ECG changes (T wave inversion, Q-T interval
prolongation, S-T segment abnormalities), phlebitis,
uveitis, optic atrophy and rarely anaphylactic shock, acute
renal failure, hepatic necrosis and bone marrow hypoplasia.
Management
Dermal
1. If possible the patient should remove soiled clothing and wash
him/herself.
2. Wash contaminated hair and skin with soap and copious amounts of
water.
3. Pay special attention to skin folds, fingernails and ears.
4. A physician may need to examine the area if irritation or pain
persists after washing.
5. Steroids may be used to treat areas of contact dermatitis.
Ocular
1. Immediately irrigate the affected eye thoroughly with tepid water
or 0.9 per cent saline for at least 10-15 minutes.
2. Any particles lodged in the conjunctival recesses should be
removed.
3. Continue irrigation with saline infusion using drip tubing.
4. Repeated instillation of local anaesthetic (eg amethocaine) may
reduce discomfort and help more thorough decontamination.
5. Corneal damage may be detected by instillation of fluorescein.
6. Patients with corneal damage and those whose symptoms do not
resolve rapidly should be referred for ophthalmological
assessment.
Ingestion
Minor ingestions (very mild or no symptoms):
1. Gastrointestinal decontamination is unnecessary.
2. Symptomatic and supportive measures only.
Moderate/substantial ingestions:
1. Gastric lavage should be considered only if the patient presents
within one hour; its value is unproven.
2. Symptomatic and supportive measures as dictated by the patient's
condition.
3. Monitor the ECG, biochemical and haematological profiles.
4. Collect urine and blood for antimony concentration measurements
to confirm diagnosis although these assays are not widely
available. Check with NPIS.
5. Chelation therapy with dimercaprol, DMSA or DMPS may be
considered; seek specialist advice from an NPIS physician.
Inhalation
Acute exposure
1. Remove from exposure.
2. Secure cardiorespiratory stability.
3. Perform a chest X-ray in symptomatic patients.
4. Treat symptomatically.
5. If significant respiratory symptoms occur investigate for
systemic toxicity: ECG, biochemical and haematological profiles
and blood and urine samples for antimony concentration
determination.
Chronic exposure
1. Investigate as for other causes of pneumoconiosis.
2. Obtain blood and urine for antimony concentration measurements to
confirm diagnosis. However, these assays are not widely
available. Check with NPIS.
3. Consider the possibility of systemic toxicity.
Injection
- Discontinue therapy if adverse effects occur and monitor as
above.
References
Bailly R, Lauwerys R, Buchet JP, Mahieu P, Konings J.
Experimental and human studies on antimony metabolism: their relevance
for the biological monitoring of workers exposed to inorganic
antimony.
Br J Ind Med 1991;48: 93-7.
Hepburn NC, Nolan J, Fenn L, Herd RM, Neilson JM, Sutherland GR,
Fox KA.
Cardiac effects of sodium stibogluconate: myocardial,
electrophysiological and biochemical studies.
QJM 1994; 87: 465-72.
Iffland R, Bosche G.
[Therapy and clinicotoxicologic follow-up of tartar emetic poisoning
caused by an ant insecticide in a small child].
Monatsschrift Kinderheilkunde 1987; 135: 227-30.
Lauwers LF, Roelants A, Rosseel M, Heyndrickx B, Baute L.
Oral antimony intoxications in man.
Crit Care Med 1990; 18: 324-6.
Miller JM.
Poisoning by antimony: a case report.
South Med J 1982; 75: 592.
Renes LE.
Antimony poisoning in industry.
Arch Ind Hyg Occup Med 1953; 7: 99-108.
White Jr GP, Mathias CGT, Davin JS.
Dermatitis in workers exposed to antimony in a melting process.
J Occup Med 1993; 35: 392-5.
Winship KA.
Toxicity of antimony and its compounds.
Adverse Drug React Acute Poisoning Rev 1987; 2: 67-90.
Substance name
Antimony potassium tartrate
Origin of substance
Manufactured from potassium bitartrate and metallic antimony in
the presence of nitric acid or solid antimony oxide.
(MERCK, 1996).
Synonyms
Antimonate (2)-, bis(mu-tartrato (4-)) di-, dipotassium,
trihydrate
Antimonyl potassium tartrate
ENT 50,434
Potassium antimony tartrate
Potassium antimonyl tartrate
Potassium antimonyl d-tartrate
Tartaric acid, antimony potassium salt
Tartar emetic
Tartarized antimony
Tartrated antimony
Tartox (RTECS, 1997)
Chemical group
A compound of antimony, a group V A element.
Reference numbers
CAS 28300-74-5 (DOSE, 1992)
RTECS CC6825000 (RTECS, 1997)
UN 1551 (DOSE, 1992)
HAZCHEM 2X (DOSE, 1992)
Physicochemical properties
Chemical structure
K2 (Sb2 (C4H4O6)2)3H2O
(DOSE, 1992)
Molecular weight
667.86 (DOSE, 1992)
Physical state at room temperature
Solid (CHRIS, 1997)
Colour
White (CHRIS, 1997)
Odour
Odourless (HSDB, 1997)
Viscosity
NIF
pH
Aqueous solution is slightly acidic. (MERCK, 1996)
Solubility
Water: 83 g/L. (MERCK, 1996)
Soluble in glycerol. (DOSE, 1992)
Insoluble in alcohol. (MERCK, 1996)
Autoignition temperature
NIF
Chemical interactions
Trivalent antimony compounds tend to form explosive mixtures with
hot perchloric acid. (HSDB, 1997)
Major products of combustion
Antimony and potassium oxide. (SAX'S, 1996)
Explosive limits
NA
Flammability
Not flammable (CHRIS, 1997)
Boiling point
NIF
Density
2.6 at 20°C (CHRIS, 1997)
Vapour pressure
NIF
Relative vapour density
NIF
Flash point
NA
Reactivity
NIF
Uses
As a mordant in the leather and textile industry.
In treatment of infections caused by Schistosoma japonicum.
As a spray on gladiolus and citrus for control of thrips.
An ingredient in liquid baits used to attract and kill wasps,
moths and yellow jackets.
Pesticide.
Used as a parasiticide, ruminatoric and an expectorant in
animals.
(MERCK, 1996; HSDB, 1997)
Hazard/risk classification
Index no. (Antimony compounds) 051-003-009
Risk phases
Xn; R20/22 - Harmful by inhalation and if swallowed.
Safety phrases
S(2-) S22 - Keep out of reach of children. Do not breathe dust
(if appropriate).
EEC No. NIF (CHIP2, 1994)
INTRODUCTION AND EPIDEMIOLOGY
Antimony potassium tartrate is a trivalent antimony compound commonly
known as tartar emetic. It is used mainly as an industrial chemical
and as a pesticide.
Historically, the systemic administration of antimony compounds has
been used in the treatment of many conditions including syphilis,
whooping cough and gout and topical antimony compounds were believed
to improve herpetic lesions, leprosy, mania and epilepsy. Antimony has
been used also as an emetic, a decongestant and a sedative and still
has a role in the treatment of tropical infections. However, trivalent
antimony therapy has generally been superseded by less toxic
treatment.
Antimony potassium tartrate is the most potent and most toxic of the
trivalent antimony compounds. Adverse effects are associated with
therapeutic use and the accidental ingestion of pesticides.
MECHANISM OF TOXICITY
The mechanism of toxicity of antimony compounds is unclear but may
involve disruption of thiol proteins via binding to sulphydryl groups
(de Wolff, 1995).
TOXICOKINETICS
Absorption
Antimony compounds may be absorbed by inhalation and ingestion, though
gastrointestinal absorption in man is poor necessitating parenteral
administration of antimony pharmaceuticals.
Distribution
Absorbed trivalent antimony readily enters red blood cells and
accumulates primarily in the spleen, liver and bone (IPCS, 1996).
Lauwers et al (1990) estimated that the total body antimony pool in a
patient who died following accidental antimony potassium tartrate
ingestion was only five per cent of the ingested dose with high
antimony concentrations in the liver, gall bladder and
gastrointestinal mucosa. This is consistent with antimony undergoing
enterohepatic circulation (see below).
Excretion
Antimony compounds are eliminated mainly in the urine, with small
amounts appearing in faeces via bile after conjugation with
glutathione. A significant amount of antimony excreted in bile
undergoes enterohepatic circulation (Bailly et al, 1991). Rees et al
(1980) demonstrated that some 80-90 per cent of an intramuscular dose
of sodium stibogluconate was recovered in the urine within six hours
of administration. However, even some 6-24 months after parenteral
antimony therapy, Mansour et al (1967) reported increased urine
antimony concentrations (range 5.8-145.3 µg/L) compared to untreated
controls (range 2.9-9.1 µg/L).
Gerhardsson et al (1982) reported significantly higher lung antimony
(p<0.001) concentrations in 40 deceased smelter and refinery workers
who had been exposed to antimony for some 30 years, compared to 11
unexposed controls. The time from last exposure to death varied from
0-23 years. The antimony concentration in liver and kidney was not
significantly different between the two groups, suggesting that
following occupational inhalation antimony may be retained in the lung
for several years without significant systemic distribution.
Kentner et al (1995) estimated a renal elimination half-life of four
days following occupational inhalation of antimony trioxide and
stibine in 21 employees of a starter battery manufacturing plant.
CLINICAL FEATURES: ACUTE EXPOSURE
Dermal exposure
Antimony and its compounds are skin irritants although antimony
dermatitis typically occurs during chronic occupational exposure (see
below) (Poisindex, 1997).
Ocular exposure
Exposure to high concentrations may produce severe eye irritation.
Ingestion
Gastrointestinal toxicity
In 1982 Miller recounted the case of the author Oliver Goldsmith who
died after ingesting a mixture of antimony trioxide and antimony
potassium tartrate. The estimated dose was 132-198 mg antimony. He
succumbed after 18 hours severe vomiting and diarrhoea.
More recently, Lauwers et al (1990) reported four adults who presented
with abdominal pain, nausea, vomiting and diarrhoea having mistaken
"tartar emetic" (antimony potassium tartrate) for "cream of tartar".
Three of them made an uneventful recovery but the fourth died from
haemorrhagic gastritis complicated by cardiorespiratory failure.
A report in the German literature has described a three year-old child
who survived ingestion of 50 mL of a liquid ant killer containing 2.3
g antimony potassium tartrate. However, the features, treatment and
antimony concentrations were not given in the English abstract
(Iffland and Bosche, 1987).
Cardiovascular and peripheral vascular toxicity
Electrocardiographic abnormalities are associated typically with
chronic antimony exposure. Following acute antimony ingestion two
patients had "moderate bradyrhythmic dysfunctions" at presentation
(Lauwers et al, 1990).
Phlebitis occurred in four patients who accidentally ingested antimony
potassium tartrate (Lauwers et al, 1990).
Inhalation
Pulmonary toxicity
Dusts and fumes of antimony and its compounds are irritant to the
respiratory tract and mucous membranes and inhalation causes
conjunctivitis, laryngitis, pharyngitis, tracheitis, rhinitis and
bronchitis (Renes, 1953; Taylor, 1966). Metal fume fever has been
described (Anonymous, 1984) though less frequently than following
exposure to zinc oxide.
There may be radiological evidence of pneumonitis which resolves upon
removal from exposure (Renes, 1953).
Injection
Hepatotoxicity
A 27 year-old woman with cutaneous leishmaniasis developed a transient
rise in alanine aminotransferase activity (to 2.4 times the upper
limit of normal) when she was inadvertently given ten times the
intended dose of parenteral pentavalent sodium stibogluconate
(Herwaldt et al, 1992). However, hepatotoxicity is observed more
typically during prolonged therapy with antimony pharmaceuticals.
Cardiovascular toxicity
No cardiovascular complications arose in a patient who accidentally
was given ten times the intended intravenous dose of sodium
stibogluconate (Herwaldt et al, 1992).
CLINICAL FEATURES: CHRONIC EXPOSURE
Dermal exposure
Dermatitis following contact with antimony compounds is well described
(McCallum, 1989).
Typical lesions arise on the arms, legs and in the flexures, sparing
the face, hands and feet (Renes, 1953; McCallum, 1989).
Papules and pustules predominate around sweat and sebaceous glands
with areas of eczema and lichenification. These so-called "antimony
spots" occur mainly in the summer (McCallum, 1989).
White et al (1993) described three cases of occupational antimony
dermatitis following several months exposure to antimony dust and
antimony trioxide fumes. Two of these patients also experienced
frequent nose bleeds. Both problems resolved when exposure ceased. In
one patient patch testing for antimony was negative and in another the
urine antimony concentration was 53.2 µg/L ('normal' < 1.0 µg/L).
Positive patch testing to antimony trioxide has been noted in
enamellers and decorators in the ceramics industry (Motolese et al,
1993).
Inhalation
Pulmonary toxicity
Chronic occupational exposure to antimony and its compounds may cause
"antimony pneumoconiosis" (McCallum, 1989). Typical radiological
findings include diffuse, dense, punctate non-confluent opacities
predominately in the middle and lower lung fields, sometimes
associated with pleural adhesions (Potkonjak and Pavlovich, 1983).
These changes developed after at least ten years working in an
antimony smelting plant where the dust contained nearly 90 per cent
antimony trioxide with some antimony pentoxide and small amounts (up
to five per cent) of silica (Potkonjak and Pavlovich, 1983). Cough (in
31 of 51 subjects) and exertional breathlessness (in 26 cases) were
the symptoms most frequently reported with wheeze, chest pain,
generalized weakness or conjunctivitis in a minority. Nine workers had
obstructive lung function defects with a combined
restrictive/obstructive picture in five cases but no isolated
restrictive defects or radiological evidence of diffuse fibrosis.
Perforation of the nasal septum has been described in antimony workers
but these cases probably have involved concomitant exposure to arsenic
(McCallum, 1989). There were no cases of nasal perforation in 51
workers employed at an antimony smelter for 9-31 years (mean 17.9
years) (Potkonjak and Pavlovich, 1983).
Brieger et al (1954) attributed ECG T-wave changes and sudden deaths
to antimony-induced cardiotoxicity following occupational exposure to
antimony trisulphide although the reliability of this study has been
criticized (McCallum, 1989).
Injection
Dermal toxicity
Davis (1968) reported antimony dermatitis in some four per cent of 160
patients treated with antimony-containing drugs.
Gastrointestinal toxicity
Patients treated for some one to two weeks with parenteral antimony
compounds frequently reported anorexia, nausea and vomiting with some
complaints of abdominal pain, a metallic taste and diarrhoea (Davis,
1968).
Pancreatitis also has been reported as a complication of parenteral
therapy with stibogluconate or meglumine antimonate (McCarthy et al,
1993; de Lalla et al, 1993; Gasser et al, 1994).
Hepatotoxicity
Parenteral treatment with antimony compounds has caused hepatic
necrosis although reversible elevations of liver enzyme activities are
more typical (Winship, 1987; Saenz et al, 1991; Hepburn et al, 1993).
Nephrotoxicity
Parenteral antimony therapy has caused acute tubular necrosis (Balzan
and Fenech, 1992; Rai et al, 1994a; Rai et al, 1994b).
Renal tubular acidosis has also been described (Horber et al, 1991).
In a review of 92 patients with visceral leishmaniasis (kala-azar)
treated with sodium stibogluconate, two showed evidence of renal
toxicity with casts and proteinuria although these patients also were
receiving intramuscular pentamidine, another recognized renal toxin
(Chunge et al, 1984).
Cardiovascular and peripheral vascular toxicity
ECG changes following exposure to antimony compounds are seen
typically in patients with leishmaniasis or schistosomiasis who have
been treated with parenteral antimony compounds. Typical features
include T wave inversion or amplitude reduction, Q-T interval
prolongation and S-T segment abnormalities (Davis, 1968; Chulay et al,
1985; Henderson and Jolliffe, 1985). These effects usually reverse
when treatment is discontinued.
In 12 soldiers with cutaneous leishmaniasis treated with sodium
stibogluconate Hepburn et al (1994) found that although a reversible
decrease in T-wave amplitude occurred during treatment there were no
significant changes in echocardiographic indices of left ventricular
function, arrhythmia frequency or heart-rate variability. The authors
concluded that 20 mg/kg/day sodium stibogluconate for 20 days had no
cardiac side-effects in most fit, young patients.
Gupta (1990) similarly noted that T-wave changes induced by antimony
therapy were not associated with a deterioration in cardiac function.
In a review of 160 patients with schistosomiasis treated with
antimony-containing drugs (Davis, 1968) retrosternal chest pain was
reported by 27 individuals. In three cases this was associated with
acute vascular collapse immediately after intravenous drug
administration (after the first dose in one case) suggesting an
anaphylactic-type response.
Phlebitis occurred in 31 patients receiving intravenous sodium
stibogluconate in the treatment of visceral leishmaniasis (Chunge et
al, 1984) and in one patient administered antimony sodium tartrate in
the treatment of urinary schistosomiasis (Davis, 1968).
Neurotoxicity
Acute hydrocephalus in association with significant ocular toxicity
(see below) occurred in a child following 23 antimony potassium
tartrate injections (Grant and Schuman, 1993).
Rai et al (1994b) described combined ninth and tenth cranial nerve
palsies in a patient with kala-azar treated with parenteral
stibogluconate. There was significant improvement within two weeks of
cessation of treatment.
Reversible peripheral neuropathy associated with sodium stibogluconate
therapy has been reported also (Brummitt et al, 1996).
Haemotoxicity
Mallick (1990) described bone marrow hypoplasia as a complication of
sodium stibogluconate administration. Haematological indices improved
significantly following treatment withdrawal and steroid therapy.
Other authors have described leucopenia (Hiçsönmez et al, 1988; Saenz
et al, 1991) or recurrent episodes of thrombocytopenia (Braconier and
Miörner, 1993) during parenteral antimonial therapy though no bone
marrow biopsies were performed.
Chunge et al (1984) reported epistaxis in 13 patients receiving
parenteral antimony-containing drugs, in three cases associated with
pancytopenia.
Musculoskeletal toxicity
Myalgia and arthralgia are reported frequently by patients with
leishmaniasis or schistosomiasis treated with parenteral antimony
compounds (Davis, 1968; Winship, 1987; Castro et al, 1990; Saenz et
al, 1991).
Ocular toxicity
In an early case report cited by Grant and Schuman (1993) a child
developed acute onset bilateral blindness with fixed dilated pupils
following 23 antimony tartrate injections. There was clinical evidence
of optic neuritis with papilloedema and subsequent permanent optic
atrophy.
Forsyth (1958) reported one patient who developed transient retinal
haemorrhages and exudates and another in whom the fundus was described
as 'granular' following parenteral sodium antimony tartrate therapy
for schistosomiasis. Visual acuity was diminished in both cases but
returned to normal within six months.
Three children who received repeated courses of parenteral tartar
emetic in the treatment of schistosomiasis developed optic atrophy
(Kassem et al, 1976).
In a review of 92 patients with visceral leishmaniasis treated with
parenteral stibogluconate, six developed uveitis and two retinal
haemorrhages after completion of treatment and apparent cure (Chunge
et al, 1984).
MANAGEMENT
Dermal exposure
Ensure adequate self protection before attempting treatment. If
possible the patient should remove any contaminated clothing
him/herself. Affected areas of skin should be washed with copious
quantities of water. Pay special attention to skin folds, fingernails
and ears. The most effective treatment for irritant antimony
dermatitis is removal from exposure.
Ocular exposure
Irrigate immediately with lukewarm water or preferably saline for at
least 10-15 minutes. A local anaesthetic may be indicated for pain
relief and to overcome blepharospasm. The use of fluorescein allows
detection of corneal damage. Specialist ophthalmological advice should
be sought if any significant abnormality is detected on examination
and in those whose symptoms do not resolve rapidly.
Ingestion
Following substantial ingestion of an antimony compound spontaneous
vomiting is likely but if this does not occur gastric lavage may be
considered if presentation is within the first hour. There are no data
to confirm that charcoal adsorbs antimony. Other symptomatic and
supportive measures should be dictated by the patient's condition. An
ECG should be performed and biochemical and haematological profiles
monitored. Blood and urine antimony concentrations are not widely
available but may be of interest retrospectively to confirm systemic
uptake.
Inhalation
Removal from exposure and measures to secure cardiorespiratory
stability are the priority following acute inhalation of antimony
compounds. An ECG should be performed. Respiratory symptoms in those
with possible chronic antimony toxicity should be investigated as for
other cases of pneumoconiosis. Urine antimony concentrations may be
useful to monitor the initial extent of and subsequent reduction in
exposure but these assays are not widely available.
Antidotes
Dimercaprol (British anti-lewisite, BAL) (Braun et al, 1946; Thompson
and Whittaker, 1947), dimercaptosuccinic acid (DMSA, Succimer)
(Basinger and Jones, 1981) and dimercaptopropane sulphonate (DMPS,
Unithiol) (Basinger and Jones, 1981; Hruby and Donner, 1987) have
antidotal activity in experimental systemic antimony poisoning (see
below). These findings have not been confirmed in controlled studies
in man.
Dimercaprol
In vitro studies
Using the pyruvate oxidase system of pigeon brains as a test model,
dimercaprol in a molar ratio of 6:1 dimercaprol: antimony was able to
protect the enzyme system from inhibition by several antimony salts
(Thompson and Whittaker, 1947).
Animal studies
The LD50 of intramuscular antimony tartrate administered to rabbits
was raised from 90 mg Sb/kg in controls to 160 mg Sb/kg in animals
treated with intramuscular dimercaprol (30 mg/kg one hour after
intoxication followed by 15 mg/kg at six, 24 and 48 hours) (Braun et
al, 1946). A total of 45 controls received 50-200 mg/kg antimony
tartrate with 56 treated animals receiving 125-200 mg/kg.
Clinical studies
Four adults with antimony poisoning following the inadvertent
consumption of antimony potassium tartrate were treated with
intramuscular dimercaprol 200-600 mg daily. Three patients made an
uneventful recovery but the fourth, who had a history of
cardiorespiratory disease, died on day three. There were no
pre-chelation antimony excretion data but in two survivors maximum
antimony urine concentrations of 1000 µg/L and 1500 µg/L were reported
some 36 and 72 hours after poisoning respectively. Urine volumes were
not stated (Lauwers et al, 1990).
Bailly et al (1991) reported a 24 year-old woman who made an
uneventful recovery after ingesting an undetermined amount of antimony
trisulphide. She was treated with dimercaprol 200 mg tds for five days
but there was no evidence of enhanced urinary antimony elimination
with therapy.
DMSA
Animal studies
DMSA was given intraperitoneally to mice at a molar ratio of 10:1
DMSA: antimony twenty minutes after administration of potassium
antimonyl tartrate (120 mg/kg; twice the LD50). The survival ratio
was 28/30 (Basinger and Jones, 1981).
Clinical studies
There are no human data.
DMPS
Animal studies
DMPS has been shown to be an effective chelating agent in mice
following intraperitoneal administration of potassium antimonyl
tartrate (120 mg/kg; twice the LD50). The survival rate was 19/30
when intraperitoneal DMPS was given twenty minutes after intoxication
at a molar ratio of 10:1 DMPS: antimony. However, DMSA was
significantly more effective under these conditions (see above)
(Basinger and Jones, 1981).
Clinical studies
There are no human data.
Antidotes: Conclusions and recommendations
1. Clinical data regarding antimony chelation are scarce.
2. Dimercaprol effectively chelates antimony but has been superseded
by the less toxic thiol antidotes DMPS and DMSA.
3. In limited animal studies DMSA is a more effective antimony
chelator than DMPS.
4. Parenteral or oral DMSA therapy may be considered in antimony
potassium tartrate poisoning. The discussion of individual cases
with a NPIS physician is recommended.
MEDICAL SURVEILLANCE
Improved occupational health measures have reduced industrial airborne
antimony concentrations significantly but monitoring of ambient air
antimony concentrations remains important in some industries (Bailly
et al, 1991; Kentner et al, 1995).
Routine examination of the skin for "antimony spots" and chest
radiography for evidence of pneumoconiosis may also be useful. The
potential risk of pulmonary carcinogenicity should be remembered (see
below).
Although Bailly et al (1991) found that urine antimony excretion among
workers exposed to airborne antimony pentoxide and sodium antimoniate
correlated to the intensity of exposure, a recent publication from the
European Commission concluded "no indicator of effect is available"
for biological monitoring of antimony (Apostoli et al, 1994).
Normal concentrations in biological fluids
"Normal" serum and urine antimony concentrations are quoted as
approximately 3 µg/L and 0.8 µg/L respectively (Poisindex, 1997).
OCCUPATIONAL DATA
Maximum exposure limit
Antimony and compounds: Long-term exposure limit (8 hour TWA reference
period) 0.5 mg/m3 (Health and Safety Executive, 1997).
OTHER TOXICOLOGICAL DATA
Carcinogenicity
There is some evidence that occupational antimony exposure is
associated with an increased risk of lung cancer although frequent
concomitant exposure to arsenic and other heavy metals precludes a
definitive conclusion about its carcinogenic potential (Gerhardsson et
al, 1982; McCallum, 1989; Gerhardsson and Nordberg, 1993; Jones 1994;
Schnorr et al, 1995).
Antimony also has been implicated in the aetiology of bladder tumours
in patients with schistosomiasis who have been treated with antimony
compounds (Winship, 1987).
Reprotoxicity
In the Russian literature women occupationally exposed to antimony
aerosols were reported to have a higher incidence of spontaneous
abortion, premature births and menstrual disorders. Antimony was
present in the blood, urine, placentae, amniotic fluid and breast milk
of these women. Further details were not available in the English
abstract (Belyaeva, 1967).
Genotoxicity
NIF
Fish toxicity
NIF
EEC Directive on Drinking Water Quality 80/778/EEC
Maximum admissible concentration 10 µg/L, as antimony (DOSE, 1992).
WHO Guidelines for Drinking Water Quality
Provisional guideline value 5 µg/L, as antimony (WHO, 1993).
AUTHORS
WN Harrison PhD CChem MRSC
SM Bradberry BSc MB MRCP
JA Vale MD FRCP FRCPE FRCPG FFOM
National Poisons Information Service (Birmingham Centre),
West Midlands Poisons Unit,
City Hospital NHS Trust,
Dudley Road,
Birmingham
B18 7QH
UK
This monograph was produced by the staff of the Birmingham Centre of
the National Poisons Information Service in the United Kingdom. The
work was commissioned and funded by the UK Departments of Health, and
was designed as a source of detailed information for use by poisons
information centres.
Date of last revision
28/1/98
REFERENCES
Anonymous.
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