Selenium Nutritional, Toxicologic, and Clinical Aspects ANNA M
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160 Articles Selenium Nutritional, Toxicologic, and Clinical Aspects ANNA M. FAN, PhD, Berkeley, and KENNETH W. KIZER, MD, MPH, Sacramento, California This is one ofa series ofarticles from western state public health departments. Despite the recent findings ofenvironmental contamination, selenium toxicosis in humans is exceedingly rare in the United States, with the few known cases resulting from industrial accidents and an episode involving the ingestion of superpotent selenium supplements. Chronic selenosis is essentially unheard of in this country because of the typical diversity of the American diet. Nonetheless, because ofthe growing public interest in selenium as a dietary supplement and the occurrence ofenvironmental selenium contamination, medical practitioners should be familiar with the nutritional, toxicologic, and clinical aspects of this trace element. (Fan AM, Kizer KW: Selenium-Nutritional, toxicologic, and clinical aspects. West J Med 1990 Aug; 153:160-167) Since the recognition of the nutritional essentiality of and other parts of the world.4 Highly seleniferous soils selenium (Se) in animals in 1957, there has been ever- yielding selenium-toxic plants (such as Astragalus bisulca- increasing interest in this trace element. This interest has tus) are widespread in South Dakota, Wyoming, Montana, heightened in the past decade concomitant with the recog- North Dakota, Nebraska, Kansas, Colorado, Utah, Arizona, nition of selenium's essential nutritional role in humans and New Mexico. Soil containing high selenium concentra- and reports of selenium toxicity among humans. Interest in tions but not yielding toxic plants is found in Hawaii. selenium has been further aroused recently by the findings of elevated levels of this compound in certain soils and wa- Chemical Forms ter sources in the western United States, leading to adverse Selenium is a nonmetallic element chemically related to effects on fish and wildlife (T. Harris, "Toxic Chemicals sulfur. It occurs naturally in four oxidation states: elemental Threaten West," The Sacramento Bee, September 8, 1985, selenium, selenite, selenide, and selenate.3 The valence pp Al, A16-A18, A20).12 state affects selenium's toxicity and bioavailability. Selenium occurs naturally in various types of soil and can leach into agricultural drain water. This has occurred in Industrial and Commercial Uses the San Joaquin Valley of California, where evaporation Selenium is used in semiconductor research (aluminum, pond drain water containing elevated levels of selenium has bismuth, and indium selenide), in the manufacture of glass been associated with adverse reproductive and other effects (ammonium selenite, arsenic hemiselenide), in photocon- in aquatic birds at the Kesterson National Wildlife Refuge.2 ductors, semiconductors, photoelectric cells, and rectifiers Similarly, in California's Salton Sea, Grassland Water Dis- (cadmium selenide), and in electron emitters (calcium se- trict, Tulare Lake Basin, and Suisun Bay, elevated levels of lenide); as a catalyst in Kjeldahl digestions (cupric se- selenium have been found in fish and aquatic birds, necessi- lenide), as a chemical reagent (potassium selenate), in vet- tating the issuance of health advisories by the California erinarian remedies for eczemas and fungal infections, and Department of Health Services-that is, recommendations as an antidandruff agent in shampoos for human use (sele- to restrict the consumption of fish and game birds from nium disulfide); in the manufacture of other selenium com- these areas. Selenium-rich sediments also have been re- pounds, and as a reagent for alkaloids (selenium dioxide); ported in wildlife refuges in Arizona, New Mexico, Utah, and as a veterinary therapeutic agent (sodium selenate, so- Montana, Idaho, and South Dakota (T. Harris, The Sacra- dium selenite).5 Radioactive nucleotides of selenium are mento Bee, Sep 8, 1985). These findings have caused con- used as biologic tracers in radiologic diagnostic cern among health and wildlife personnel, as well as the procedures-selenocysteine Se 75 and selenomethionine Se agriculture industry, and have been widely reported in the 75 are used for pancreatic imaging. Selenium is also used as media, at times causing considerable alarm among the pub- a dietary supplement for some farm animals (sodium se- lic. Conversely, exaggerated claims about the health bene- lenite), and it is taken as a nutritional supplement by hu- fits of selenium have been made in the popular press. In this mans (mostly selenium-enriched yeast products). Based on article we review the nutritional, toxicologic, and clinical data available to the California Department of Health Ser- aspects of selenium in an effort to assist physicians with vices, we estimate that more than 250,000 Californians take questions and concerns about this compound. selenium as a nutritional supplement. Occurrence Environmental Sources of Selenium Exposure Selenium is a naturally occurring element found in rock, Water shale, sandstone, limestone, coal, soil, surface water, and Selenium, in the forms of selenite and selenate, is found vegetation.3 It occurs in relatively high concentrations in in water, principally as a result ofleaching from seleniferous many of the soils of the US, especially the western states, rocks and soils.' At pH 6.3 to 6.7, precipitation of insoluble From the Pesticide, Food, and Water Toxicology Unit, Hazard Evaluation Section, California Department of Health Services, Berkeley (Dr Fan), and the California Department of Health Services, Sacramento (Dr Kizer). Reprint requests to Anna M. Fan, PhD, California Department of Health Services, Hazard Evaluation Section, 2151 Berkeley Way, Berkeley, CA 94704. - o e THE WESTERN JOURNAL OF MEDICINE AUGUST 1990 153 2 161 ferric selenite occurs in the presence of iron. At pH 8, it is diet is deficient in vitamin E. Similarly, caries formation oxidized to soluble selenate. The federal and state maxi- may be increased if lower levels of selenium are consumed mum contaminant level established for selenium in drink- during the development of teeth. ing water is 10 parts per billion. Water is generally not a Humans biologically significant source of intake. Toxicity from acute inhalation or dermal contact. Acute Food human selenium toxicosis has been reported from indus- The concentration of selenium in plant tissues depends trial and other accidental exposures.'0 For example, inhal- on the concentration and availability of selenium in the soil ing selenium fumes, selenium dioxide, or hydrogen selenide where the plants are grown. Selenium-accumulator plants causes intense irritation of the mucous membranes of the grow only in soil containing high levels of selenium- to 50 eyes and upper respiratory tract, producing ophthalmor- parts per million (ppm)-and accumulate concentrations of rhea and ophthalmodynia, coryza, hoarseness, coughing, as much as 1,000 to 10,000 mg per kg.5 and sneezing.'7"0 Headache, dizziness, dyspnea, fatigue, Selenium is generally found at levels of less than 1 ppm nausea, vomiting, a bitter taste in the mouth, and a garlic in food, wet weight. The major dietary sources of human odor of the breath may also characterize acute inhalational intake are meat, poultry, grain and grain products, and sea- selenosis. food. The dietary selenium intake for the US population has Skin exposure to selenium may cause severe local irrita- been estimated to be in the range of 60 to 216 jg per adult tion, producing painful burning, erythema, and occasion- person per day.6 A daily intake of 50 to 200 jg of selenium ally allergic dermatitis. The severity of response depends on for adults is considered adequate and safe by the Food and the chemical form of the selenium compound. The most Nutrition Board of the National Academy of Sciences.7 severe responses occur after exposure to the highly poison- Lower intake levels are recommended for children younger ous hydrogen selenide. Reactions to selenium oxychloride, than 7 years. dioxide, and hexafluoride are less severe. Elemental sele- nium and selenium sulfides are generally considered non- Air toxic. Most urban areas have atmospheric particulate sele- Ingestion. A number of instances of acute selenosis from nium concentrations ranging from 0.1 to 10 ng per m3, con- the ingestion of selenium-containing products or foodstuff tributing a biologically insignificant exposure. The occupa- have occurred in recent years (Table 1).121-6 Illustrative of tional threshold limit value for inorganic selenium is 0.2 mg these situations was a case in New Zealand of acute seleno- per m3.8 sis from ingesting sheep drench containing 22.3 mg Se per Toxicity kilogram as sodium selenate."1 In this case, a young girl Animals ingested 1,160 mg of selenium. Her initial serum selenium The toxicity of selenium has been recognized since the concentration was 3,100 /tg per liter, and the initial 24-hour 1930s when it was discovered that certain seleniferous soils urine collection showed 680 /4g per ml. She had a strong produced plants having a high selenium content.39 A few garlic odor to her breath and frequent loose, grey bowel species of selenium-accumulator plants characteristically movements. She was treated with gastric lavage, diuresis, accumulate extremely high levels of selenium in the form of and the administration of vitamin C and dimercaprol. She nonprotein selenoamino acids such as Se-methyl- suffered no apparent sequelae, although biochemical tests selenocysteine and can cause acute toxic reactions