Dermal and Ophthalmic Exposure
Dermal exposure to selenious acid or to selenium dioxide (which is converted to selenious acid) and to selenium oxychloride (a vesicant that is hydrolyzed to hydrochloric acid) causes significantly painful caustic burns.10 Excruciating pain may result from accumulation under fingernails. Corneal injury with severe pain, lacrimation, and conjunctival edema is reported after exposure to selenium dioxide sprayed unintentionally into the face.24 In chronic exposures, "rose eye," a red discoloration of eyelids with palpebral conjunctivitis, is also described.
When inhaled, all selenium compounds have the potential to be respiratory irritants. In general, inhaled elemental selenium dusts are less injurious than compounds converted to selenious acid. Hydrogen selenide inhalation toxicity is reported throughout the industrial literature.6 Hydrogen selenide is oxidized to elemental selenium, so acutely, toxic exposures are limited to confined spaces where the hazardous gas may accumulate; however, similar to hydrogen sulfide (H2S), its ability to cause olfactory fatigue, rendering the exposed persons anosmic to the toxic fumes, may prove very hazardous (see Chap. 20).6 Acute exposure to high concentrations of hydrogen selenide gas produces throat and eye pain, rhinorrhea, wheezing, and pneumomediastinum, with residual restrictive and obstructive disease that may persist years later.33
In contrast, selenium dioxide and selenium oxide fumes form selenious acid in the presence of water in the respiratory tract. Twenty-eight workers in a selenium rectifier plant were inadvertently exposed to smoke and high concentrations of selenium oxide in an enclosed area. Initial symptoms included bronchospasm with upper respiratory irritation and burning. Some acutely developed hypotension, tachycardia, and tachypnea, which resolved over 2 hours. Patients went on to develop chemical pneumonitis, fever, chills, headache, vomiting, and diarrhea. Five patients required hospitalization for respiratory support, with fever, leukocytosis, and bilateral infiltrates. All patients recovered without sequelae.44
Selenium hexafluoride is a caustic gas used in industrial settings as an electrical insulator. Its caustic properties are derived from its conversion, in the presence of water, to elemental selenium and hydrofluoric acid. Severe pain and burning of the eyes, skin, and respiratory tract similar to that seen with hydrofluoric acid exposure can occur after inhalation of selenium hexafluoride (see Chap. 105).
Acute selenium toxicity occurs after ingestion of inorganic selenium compounds, which include sodium selenite, sodium selenate, selenium dioxide, hydrogen selenide, selenic acid, and selenious acid. Selenious acid is the most toxic of these. Elemental selenium and organic selenium compounds do not cause acute toxicity.
Some authors have proposed a "triphasic" course of acute inorganic selenium toxicity, with GI, myopathic, and circulatory symptoms as the overdose progresses.39 In reality, acute inorganic selenium poisoning is often rapid and fulminant, with onset of symptoms within minutes and, in some cases, death within 1 hour of ingestion. GI symptoms are the most commonly described and the first to occur and include abdominal pain, diarrhea, nausea, and vomiting. This may be partly caused by caustic esophageal and gastric burns but does not occur in all cases. Patients may have a garlic odor. The myopathic phase is characterized by weakness, hyporeflexia, myoclonus, fasciculations, and elevated creatine phosphokinase (CPK) concentrations with normal MB fraction. Renal insufficiency is also reported and presumably results from myoglobinuria and hemolysis. More severely poisoned patients may exhibit lethargy, delirium, and coma.
Circulatory failure is the hallmark of serious inorganic selenium toxicity. Patients present with dyspnea, chest pain, tachycardia, and hypotension. The initial electrocardiogram (ECG) may demonstrate ST elevation, a prolonged QT interval, and T-wave inversions. Refractory hypotension occurs as a combined product of decreased contractility from toxic cardiomyopathy and decreased peripheral vascular resistance. Pulmonary edema, ventricular dysrhythmias, myocardial and mesenteric infarction, and metabolic acidosis all contribute to poor outcome in these patients.25,29,44 Death results from circulatory collapse in the setting of pump failure, hypotension, and ventricular dysrhythmias, often within 4 hours of ingestion.7,17,19,30,38
Other less frequent abnormalities include hypokalemia, hyperkalemia, coagulopathy, leukocytosis, hemolysis, thrombocytopenia, and metabolic acidosis with elevated lactate.34,39
The classic scenario of acute fatal inorganic selenium poisoning is in the context of selenious acid ingestion, usually as gun bluing solution. Similar toxicity may result from selenium oxide and dioxide, which are converted to selenious acid as well as sodium selenite and selenate. The underlying mechanism for this fulminant clinical syndrome is not well understood but may stem from a multifocal disruption of cellular oxidative processes and antioxidant defense mechanisms.
Chronic elemental selenium toxicity, or selenosis, has received recent attention because of reports of improperly packaged nutritional supplements. In 2008, at least 200 people were affected by a manufacturing error in a selenium-containing dietary supplement and developed diarrhea, alopecia, fatigue, and nail deformities.42 The manufacturer voluntarily recalled the product, and a Food and Drug Administration investigation revealed that the liquid supplement contained 800 μg/L instead of the 7.3 μg/L of selenium claimed on the packaging.43 A similar outbreak occurred from a super-potent supplement in 1983, affecting at least 13 patients, all of whom recovered after discontinuation of the supplement.14,35
Selenosis is similar to arsenic toxicity, with the most consistent manifestations being nail and hair abnormalities. As with arsenic toxicity, nail or hair findings alone are unlikely to be the sole evidence of selenosis, but their absence makes the diagnosis unlikely. The hair becomes very brittle, breaking off easily at the scalp, with regrowth of discolored hair and the development of an intensely pruritic scalp rash. The nails also break easily, with white or red ridges that can be either transverse or longitudinal; the thumb is usually involved first, and paronychia and nail loss may develop.27 The skin becomes erythematous, swollen, and blistered; slow to heal; and with a persistent red discoloration. Increased dental caries may occur.12 Neurologic manifestations include hyperreflexia, peripheral paresthesia, anesthesia, and hemiplegia. Although cardiotoxicity is described with both selenium deficiency and acute poisoning, no such cases are reported with human selenosis. Aside from one case described in the Chinese population, in which there were insufficient postmortem data, there have been no reported deaths from intermediate or chronic exposure.
Selenosis is implicated in a number of long-term environmental exposures. Many descriptions come from inhabitants of the Hubei province of China from 1961 to 1964, the majority of whom developed clinical signs after an estimated average consumption of 5000 μg/d of selenium (but as little as 910 μg/d) derived from local crops and vegetation.45 Inhabitants of a seleniferous area of Venezuela, consuming approximately 300 to 400 μg/d of selenium, also develop symptoms of selenium excess; however, the low socioeconomic and poor dietary status of the subjects may also contribute to their symptoms. In contrast, U.S. residents in a seleniferous area with a high selenium intake (724 μg/d) over 2 years who were compared with a control population and monitored for symptoms and laboratory abnormalities, remained asymptomatic, with only a clinically insignificant elevation of hepatic aminotransferases in the high-selenium group.22 Average selenium concentrations were serum, 0.215 mg/L; whole blood, 0.322 mg/L; and urine, 0.17 mg/L.
Selenosis is also reported in the industrial setting. Copper refinery workers demonstrate garlic odor and GI and respiratory symptoms coincident with exposure to selenium dust and fumes.15 Long before workplace biological monitoring took place, intense garlic odor of the breath and secretions was recognized as a reason to remove a worker from selenium until the odor subsided. Neuropsychiatric findings such as fatigue, irritability, and depression are reported throughout the industrial literature and are difficult to quantify. Early reports describe the selenium factory worker who "could not stand his children about him" at the end of the day.10
Although carcinogenicity is suggested by a number of animal studies, in humans, the data available suggest, if anything, an inverse correlation between selenium intake and cancer risk. The International Agency for Research on Cancer does not list selenium as a known or suspected carcinogen.2. Animal studies also suggest that selenium has embryotoxic and teratogenic properties.11 A recent large randomized controlled trial of selenium supplementation suggested an increased the risk of diabetes mellitus with the ingestion of 200 μg/day of elemental selenium-fed baker's yeast compared with placebo.41