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. Metals and the lung. Lancet 1984; 2: 903-4. Apostoli P, Porru S, Alessio L. Antimony. In: Alessio L, Berlin A, Roi R, van der Venne MT, eds. 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