Data on human toxicity of antimony are very limited, and are largely extrapolated from occupationally exposed patients and adverse effects that have occurred during treatment of leishmaniasis and schistosomiasis, and very few case reports of intentional antimony exposures.86
Workers with occupational exposures usually present with subtle clinical symptoms as chronic toxicity develops slowly over time. It is important to recognize that antimony ore contains a small concentration of arsenic, making it difficult to determine whether the effects on workers are caused by contaminants such as arsenic or by the antimony. Therapeutic side effects of antiparasitic treatment may have acute and subacute clinical manifestations, as some patients with leishmaniasis require prolonged antimonial treatment to achieve cure,116 exposing them, over time, to very large cumulative doses.
Patients with ingestions present with acute symptoms mimicking the toxicity of arsenic and other metal and metalloid salts.
The most common manifestations of antimony toxicity involve local irritation. In sufficient concentration, antimony acts as an irritant to the eyes, skin, and mucosa. Chronic exposure can cause conjunctivitis.15,43,101 Irritation of the upper respiratory tract can lead to pharyngitis and frequent nose bleeds.124
Antimony pentachloride is very irritating and can cause local dermal and mucosal burns. It reacts with water, releasing hydrochloric acid, heat, and antimony pentaoxide (Sb2O5). Following ingestion, contact with the water in saliva produces sufficient hydrochloric acid to potentially result in consequential gastrointestinal burns.
Ocular exposure to Sb2O5 can cause typical caustic injury resulting in blepharospasm, lacrimation, photophobia, and even corneal burns. Exposure to antimony trichloride fumes can cause similar ocular symptoms.50
Systemic ocular toxicity can manifest in optic atrophy, uveitis, and retinal hemorrhage with exudates resulting with diminished visual acuity.27,72 Some of these changes can be permanent.72
Thrombophlebitis is common after intravenous (IV) use of antimony, but has been reported even when poisoning occurs orally.77
Following acute exposures, antimony can rapidly produce anorexia, nausea, vomiting, abdominal pain, and diarrhea.77,122 Some patients may report a metallic taste in the mouth.5,33 It is possible to sense a garlic odor on the breath, but this might be due to concomitant arsenic exposure. In severe overdose, gastrointestinal irritation can progress to hemorrhagic gastritis.77 Workers chronically exposed to antimony dusts have a much higher incidence of gastrointestinal ulcers in comparison to controls (63 per 1000 versus 15 per 1000).19 Many patients develop pancreatitis following treatment with pentavalent antimonial agents.34,45,84 Because most cases improved despite continuation of treatment, a mechanism other than direct pancreatic toxicity is presumed. In another series, several patients with human immunodeficiency virus (HIV) who were treated with high doses of meglumine antimonate developed severe pancreatitis and died.36
In animals, antimony decreases myocardial contraction, decreases coronary vasomotor tone producing decreased systolic pressure, and causes bradycardia.32,126 The majority of reported human cardiac effects are related to the electrocardiographic (ECG) changes. Prolongation of the QT interval, inversion or flattening of T waves, and ST segment changes are frequently described during treatment of visceral leishmaniasis with pentavalent antimonial compounds (sodium stibogluconate and meglumine antimonate).26,125 Torsades de pointes was described in the patients treated with pentavalent antimonial preparations.92,115 In patients with underlying myocardial disease such as a cardiomyopathy, ECG changes can occur even at subtherapeutic antimony doses.52 These changes are not necessarily associated with deterioration in cardiac function.59 However, it is important to recognize that pentavalent antimonial drugs used for the treatment of leishmaniasis are associated with sudden deaths, probably as a result of the development of ventricular dysrhythmias.23,111
Local irritation from antimony trioxide can produce laryngitis, tracheitis, and pneumonitis.48,101,114 Pneumonitis is usually reversible after exposure ceases and can be followed radiologically.101 Acute lung injury was reported after acute exposure to antimony pentachloride.30,31
Although antimony oxides are capable of causing metal fume fever,4,42 this is much less common in comparison to exposure to zinc oxide (see Chap. 101).4,42 Antimony metal fume fever is reported to occur even with air concentrations below 5 mg/m3.29
Workers chronically exposed to antimony compounds for many years may develop "antimony pneumoconiosis."28,83 Patients present with cough, wheezing, and exertional dyspnea that can progress to obstructive lung disease. Radiologically, antimony pneumoconiosis appears as diffuse, dense, punctate nonconfluent opacities with a predominant distribution in middle and lower lung lobes with or without pleural adhesions.97
Patients treated with sodium stibogluconate can develop varied manifestations of renal toxicity ranging from renal cell casts, proteinuria, and increased blood urea nitrogen concentration27 to renal failure.6,99 Some patients can also develop renal tubular acidosis65 and acute tubular necrosis.98
Chronic therapeutic use of antimony compounds for the treatment of leishmaniasis can cause liver toxicity that can range from reversible elevations of aminotransferase concentrations to hepatic necrosis.61,64,104,126
Severe anemia was reported in HIV-positive patients during treatment with sodium stibogluconate. Bone marrow biopsy documented transient severe marrow dyserythropoiesis, followed by complete recovery on discontinuation of the therapy.63,80
Patients treated with sodium stibogluconate for visceral leishmaniasis occasionally develop thrombocytopenia.16,60,70 Rare cases of epistaxis are described during the treatment, and it is unclear if they are associated with thrombocytopenia.71 Visceral leishmaniasis itself is known to be associated with pancytopenia, probably as a result of increased destruction of peripheral blood cells.96 It may be difficult to determine whether this phenomenon is caused by disease itself or is secondary to the treatment, although some authors suggested a drug-induced immune thrombocytopenia.96
Leukopenia is frequently observed in patients treated with antimonial compounds.36,126,127 Some authors speculate that antimony-induced lymphopenia is associated with an increased frequency of herpes zoster in HIV patients.127
Antimony spots108 are papules and pustules that develop around sweat and sebaceous glands and may resemble varicella. Chronically exposed patients can develop areas of eczema and lichenification that typically occur in the summer and are usually found on the arms, legs, and in the joint creases with sparing of the face, hands, and feet.83,101 A similar skin rash was described in the 18th century after external application of antimony tartrate for medicinal use.82 Interestingly, these eruptions were usually interpreted as a sign of cure.54 It is also suggested that antimony trioxide can cause contact dermatitis.88
A patient with cutaneous leishmaniasis who was treated with sodium stibogluconate (pentavalent antimony) developed a reversible, peripheral sensory neuropathy in temporal association with treatment.20
Therapeutic use of parenteral antimonials can be associated with diffuse muscle and joint pain.22,33,104,126
In animal studies, antimony exposure causes ovarian atrophy, uterine metaplasia, and impaired conception.11 An association between spontaneous abortion and premature births is reported in women who were occupationally exposed to antimony salts. Antimony was found in the blood, urine, placenta, amniotic fluid, and breast milk of these women.11
Female rats developed lung tumors after inhalational exposure to antimony trioxide and antimony trisulfide.14,51,120 A survey among antimony smelter workers suggested an excess of lung cancer, with a latency of 20 years, in comparison to a nonexposed population. However, concomitant exposure to arsenic and its effects could not be excluded and the data were poorly or inadequately controlled for workers' smoking habits.69 Exposure to antimony oxide over 9 to 31 years did not suggest increased incidence of lung cancer in one group of workers.97 Patients with schistosomiasis have an increased incidence of bladder tumors, and antimony compounds are considered to be one potential cause.126
Both stibine and trimethylstibine are capable of damaging DNA, presumably by the generation of reactive oxygen species. No other forms of antimony tested including potassium antimony tartrate, potassium hexahydroxyantimonate, and trimethylantimony dichloride were found to be genotoxic.3