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Contaminants in soil: updated collation of toxicological data and intake values for humans Selenium Better Regulation Science Programme Science report: SC050021

ii Contaminants in soil: updated collation of toxicological data and intake values for humans. Selenium

The Environment Agency is the leading public body protecting and improving the environment in England and Wales.

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Published by: Environment Agency, Rio House, Waterside Drive, Aztec West, Almondsbury, Bristol, BS32 4UD Tel: 01454 624400 Fax: 01454 624409 www.environment-agency.gov.uk ISBN: 978-1-84911-022-8 © Environment Agency March 2009 Author(s) of this update to the report: James Hopkins and Mark Hosford Dissemination Status: Publicly available / released to all regions Keywords: Land contamination, human health, risk assessment, health criteria value, tolerable daily intake, mean daily intake, selenium Environment Agency’s Project Manager: Mark Hosford, Science Department Science Project Number: SC050021 Product Code: SCHO0309BPQO-E-P This report is printed on Cyclus Print, a 100% recycled stock, which is 100% post consumer waste and is totally chlorine free. Water used is treated and in most cases returned to source in better condition than removed. Further copies of this report are available from: The Environment Agency’s National Customer Contact Centre by emailing: [email protected] or by telephoning 08708 506506.

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The CLEA Guidance incorporates the following

1) Science Report SC050021/SR2: Human health toxicological assessment of contaminants in soil.

2) Science Report SC050021/SR3: Updated technical background to the CLEA model.

3) Science Report SC050021/SR4: CLEA Software (Version 1.04) Handbook.

4) CLEA Software version 1.04 (2009)

5) Toxicological reports and Soil Guideline Value briefings

The CLEA Guidance can help suitably qualified assessors to estimate the risk that a child or adult may be exposed to a soil concentration on a given site over a long period of exposure that may be a cause for concern to human health. The CLEA Guidance does not cover other types of risk to humans, such as fire, suffocation or explosion, or short-term and acute exposures. Nor does it cover risks to the environment or the pollution of water.

The CLEA Guidance is non-statutory. It does not purport to interpret the policies or procedures of the Environment Agency and shall not operate as a statutory licence, waiver, consent or approval from the Environment Agency. Nothing in the CLEA Guidance shall prejudice, conflict with or affect the exercise by the Environment Agency of its statutory functions, powers, rights, duties, responsibilities, obligations or discretions arising or imposed under the Environment Act 1995 or any other legislative provision enactment, bye-law or regulation.

The CLEA guidance describes the soil concentrations above which, in the opinion of the Environment Agency, there may be concern that warrants further investigation and risk evaluation for both threshold and non-threshold substances. These levels are a guide to help assessors estimate risk. It does not provide a definitive test for telling when risks are significant.

Regulators are under no obligation to use the CLEA Guidance.

Contaminants in soil: updated collation of toxicological data and intake values for humans. Selenium iii

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Executive summary This report, one of a number on the assessment of risks to human health from contaminants in soil, presents key data and expert opinions on the toxicology and intake of selenium. It provides an update to an earlier report by the Department for Environment, Food and Rural Affairs (Defra) and the Environment Agency published in March 2002.

The report is based on findings from literature searches made during February 2007 and October 2008. These findings, together with health criteria values (HCVs) derived by national, European and international expert groups, are used to recommend an oral tolerable daily intake (TDIoral) and to estimate the mean daily intake (MDI) for selenium in the UK.

Chemical overview

Selenium (Se) is a metalloid element and its chemistry exhibits many similarities to that of sulphur. Many organic compounds containing selenium have been identified in nature, with some having important metabolic roles. The wide variation in levels of naturally occurring selenium in the environment has led to both deficiency and toxicity in humans and other animal species.

Commercial uses of selenium include in the glass industry, in chemicals and pigments, in electronics and in agriculture. The major sources of selenium entering the environment include the burning of fossil fuels, the mining and refining of copper and other metals, and the manufacture of glass and electronic and photocopier components.

In the environment, the volatile selenium compounds that partition into the atmosphere include the inorganic compounds, selenium dioxide and hydrogen selenide, and the organic compounds, dimethyl selenide and dimethyl diselenide. The main forms of selenium in soil are selenate (Se6+), selenite (Se4+), and selenide (Se2-). Because of their high solubility and low adsorption tendency, selenates are very mobile. Although selenites are usually soluble in water, in acid soils selenium is usually found as selenite bound to iron and aluminium oxides in compounds of very low solubility. Elemental selenium and inorganic selenium compounds such as sodium selenite can be methylated by micro-organisms in soil, with subsequent volatilisation to the atmosphere.

Pharmacokinetics

Animal studies indicate that selenium is extensively absorbed after inhalation exposure, with the rate being dependent on chemical form and particle size. Oral studies in humans and in rats indicate about 50% to total absorption of various selenium compounds. Human studies have not identified dermal absorption of selenium compounds; however, evidence from animal studies suggests that dermal absorption may occur.

The metabolism of selenium results in its incorporation into a number of selenoproteins that include selenocysteine in their structure. Methylation of selenium is dose-dependent and is an important detoxification route at high doses. Methylation produces the trimethyl selenonium ion. The main route of excretion of selenium in humans and other animals is in urine, with the trimethyl selenonium ion being a major urinary metabolite. Faecal excretion also occurs, particularly after chronic exposure, possibly to an equivalent extent to urinary excretion when exposures are not excessive.

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Toxicity

Single oral doses of 250 mg or multiple doses of 27–31 mg selenium have produced overt signs of toxicity in humans, including gastrointestinal effects and neurological disturbances. Long-term ingestion of selenium produces a range of adverse effects (termed selenosis) in humans, including changes to the hair and nails, skin lesions and neurological effects. Daily doses of 910 µg have produced the milder signs of selenosis in Chinese adults.

Adverse reproductive and developmental effects have been produced in animals treated with selenium at doses that were also toxic to the parent animals. In general, only limited carcinogenicity studies have been reported on selenium compounds. With the exception of selenium sulphides, these have not given convincing evidence of carcinogenicity. Some selenium compounds have given indications of genotoxic effects when administered orally to laboratory animals; however, it has been suggested that the mechanism involves the production of reactive oxygen species and is likely to have a threshold.

Essentiality and deficiency

Selenium is important for an extensive range of biochemical functions within the body. These functions are mediated by at least 20 selenoproteins, such as glutathione peroxidase, which contain selenocysteine at their active site. These proteins play a key role in a number of metabolic processes including antioxidant systems, thyroid hormone metabolism, immune function and reproduction.

Selenium deficiency has been strongly associated with two widely endemic diseases in China: Keshan disease, a cardiomyopathy; and Kashin-Beck disease, a chronic osteoarthropathy. The World Health Organization (WHO) recommends that selenium intakes necessary for the maintenance of good health are 33–34 µg day-1 for adult males and 25–26 µg day-1 for adult females (35–42 µg day-1 for lactating women).

Health Criteria Values and risk assessment

The UK Expert Group on Vitamins and Minerals has estimated that a daily oral dose of 450 µg of selenium would not pose a significant risk to the health of an adult. Based on the default adult bodyweight of 70 kg, this is equivalent to 6.4 µg kg-1 bw day-1, which is recommended here as the TDIoral. The proven liver carcinogenicity in rodents of selenium sulphides means that the TDIoral is not applicable to selenium in the form of sulphides, but these are not anticipated to be prevalent in the soil environment. The milder signs of selenosis (involving changes to the nails and hair) might be expected to develop at exposures as low as twice the TDIoral, i.e. at around 13 µg kg-1 bw day-1.

There are no expert group evaluations of inhalation or dermal exposure to selenium, and data for these routes appear very limited. In view of the uncertainties around inhalation toxicity, and since oral exposure would be expected to dominate a risk assessment of selenium in soil, no TDIinh is proposed here. It is nonetheless preferable to account for inhalation exposure in the overall risk assessment of selenium. This may be achieved rudimentarily by comparing the inhalation exposure against the TDIoral.

Mean daily intakes from non-soil sources

The adult oral mean daily intake from food and water combined (MDIoral) for selenium is estimated to be 35 µg day-1, while the adult inhalation mean daily intake from ambient air (MDIinh) is estimated to be 0.06 µg day-1.

Contaminants in soil: updated collation of toxicological data and intake values for humans. Selenium vi

HCV and MDI values for selenium

Parameter Oral Inhalation

MDI (µg day-1) 35 0.06

MDI for 70 kg adult (µg kg-1 bw day-1) 0.5 0.0009

MDI for 20 kg child (µg kg-1 bw day-1) 1.3 a 0.002 a

TDI (µg kg-1 bw day-1) 6.4 Not derived a see Environment Agency (2009a) for details of MDI conversion factors.

Summary of changes to HCV recommendations

The conclusions of this report closely agree with those of the 2002 report. The TDIoral of 6.4 µg kg-1 bw day-1 proposed herein is slightly higher than the previous value of 5 µg kg-1 bw day-1 due to the availability of the new EVM evaluation of the critical data, which essentially corroborates the 2002 commentary that 5 µg kg-1 bw day-1 may be slightly conservative.

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Acknowledgements This report was initially compiled by RPS Group plc and later updated by bibra. The Environment Agency is also grateful for the valuable inputs from various government agencies and departments particularly the Department of Health, Health Protection Agency and Food Standards Agency. It would also like to thank the Medical Research Council’s Institute for Environment and Health for peer reviewing the original document written by RPS Group.

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Contents 1 Introduction 1 1.1 Update to R&D Publication TOX 10 1 1.2 Background 1 1.3 Advice on using this report 2

2 Chemical overview 4

3 Toxicity 6 3.1 Literature sources 6 3.2 Pharmacokinetics 6 3.3 Acute and subacute toxicity 7 3.4 Subchronic and chronic toxicity 8 3.5 Reproductive and developmental toxicity 9 3.6 Genotoxicity 9 3.7 Carcinogenicity 10 3.8 Summary 11

4 Essentiality and deficiency 12

5 Derivation of Health Criteria Values 13 5.1 UK Expert Group on Vitamins and Minerals 13 5.2 UK Committee on the Medical Aspects of Food and Nutrition Policy 13 5.3 EU Scientific Committee on Food 13 5.4 European Food Safety Authority 14 5.5 World Health Organization 14 5.6 US Environmental Protection Agency 15 5.7 US Agency for Toxic Substances and Disease Registry 15 5.8 Discussion 15

6 Background intake 17 6.1 Food 17 6.2 Water 17 6.3 Air 17 6.4 Other sources 18 6.5 Estimation of mean daily intakes 18

7 Conclusions 19

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References 20

List of abbreviations 26

Appendix – Literature search 27

Contaminants in soil: updated collation of toxicological data and intake values for humans. Selenium 1

1 Introduction

1.1 Update to R&D Publication TOX 10 This report presents key data and expert opinion on the human toxicology and non-soil intakes of selenium. It updates and replaces R&D Publication TOX 10 published in March 2002 (Defra and Environment Agency, 2002), taking into account:

• updates to the toxicological framework document which describes how the human toxicity of chemical soil contaminants is assessed (Environment Agency, 2009a);

• further review of the scientific literature on the toxicology of selenium and the findings and opinion of national, European and international expert groups up to February 2007 (see Appendix).

1.2 Background The main purpose of this report is to provide technical guidance to regulators and their advisors in support of the statutory regimes addressing land contamination, particularly Part 2A of the Environmental Protection Act 1990 and development control under the Town and Country Planning Acts.

Part 2A defines the term contaminated land according to whether or not it poses a significant risk to human health and/or the environment.

In relation to health effects not attributable to radioactivity, it considers land to be contaminated land where it:

“... appears to the local authority in whose area the land is situated to be in such a condition by reason of substances in, on or under the land that (a) significant harm [to human health] is being caused or there is a significant possibility of such harm being caused.”

Statutory guidance (Defra 2006) explains that significant harm to a person would include such health effects as death, disease,1 serious injury, genetic mutation, birth defects or the impairment of reproductive function. The definition of significant harm therefore encompasses a broad range of possible health outcomes from chemical exposure.

Land contamination is a material consideration within the planning regime. A planning authority has to consider the potential implications of contamination both when it is developing structure or local plans (or unitary development plans) and when it is considering applications for planning permission. Planning Policy Statement 23 (England) (PPS23) (ODPM, 2004) explains the relationship between planning and Part 2A. In the granting of planning permission for new development including permission to carry out remediation, PPS 23 states that remediation must remove unacceptable risk to human health and make the site suitable for its intended use. As a minimum, after carrying out a development and commencement of its use, the land should not be capable of being determined as contaminated land under Part 2A. 1 For the purpose of the Statutory Guidance, disease is taken to mean an unhealthy condition of the body or part of it and can include, for example, cancer, mental dysfunction, liver dysfunction or extensive skin ailments.


1.3 Advice on using this report This report reviews the key toxicological literature and expert opinion on health effects arising from exposure to selenium. It has been prepared by the Environment Agency with the support of the Health Protection Agency (HPA) and the Food Standards Agency (FSA).

This report recommends one or more Health Criteria Values (HCVs) for use in assessing the risks to health from long-term human exposure to selenium in soil. HCVs are an important part of the risk assessment process. They are used subsequently in the derivation of Soil Guideline Values (SGV), which are scientifically based generic assessment criteria used to simplify the screening of land contamination (Defra and Environment Agency, 2004). HCVs can also be used to derive site-specific assessment criteria for soil as part of any Detailed Quantitative Risk Assessment.

The HCVs set out in this report represent levels of minimal or tolerable risk from long-term human exposure to chemicals in soil. They represent a baseline and health protective position to minimise risks of significant harm. They do not represent thresholds above which there is an unacceptable intake or a significant possibility of significant harm in the context of Part 2A, but they can be a useful starting point for such an assessment (Defra, 2008). Science alone cannot answer the question of whether or not a given possibility of significant harm is significant, since what is either significant or unacceptable is a matter of socio-political judgment and the law entrusts decisions on this to the enforcing authorities (Defra, 2008).

In the context of Part 2A, an assessor using the HCVs in this report can conclude that (Defra, 2008):

• human exposure at or below the HCV is unlikely to represent a significant possibility of significant harm;

• human exposure above the HCV might represent a significant possibility of significant harm, with the significance linked to the margin of exceedance, the duration and frequency of exposure, and other factors that the enforcing authority may wish to take into account.

The information presented in this report is intended for technical professionals familiar with assessment of the risks posed to human health by land contamination. It should be read in conjunction with Science Report SC050021/SR2 Human Health Toxicological Assessment of Contaminants in Soil (Environment Agency, 2009a), which introduces and describes the terms and general technical approaches used in this review of selenium.

Although HCVs are an important quantitative tool for judging the health risks associated with a particular level of human exposure, they should not be used in isolation from the rest of the information presented in this report. Further understanding of the mechanisms of toxicity and the range of potential health effects are important to assessing the risks posed by selenium at any level of exposure, both individually and when combined with other chemicals present.

The remainder of this report is separated into the following sections.

Section 2 provides a short overview of the chemistry of selenium, its main uses and its behaviour in the environment with particular reference to soils.

Section 3 presents information obtained from the literature search on the toxicity of selenium (pharmacokinetics, acute and subacute toxicity, subchronic and chronic toxicity, reproductive and developmental toxicity, genotoxicity and carcinogenicity).


Section 4 outlines the body’s essential need for selenium together with evidence of the effects of deficiency, as well as the possible benefits of selenium in protecting against disease.

Section 5 sets out the HCVs for selenium derived by various expert groups worldwide.

Section 6 gives estimates of background levels of selenium in food and water, air and other sources.

Section 7 presents the conclusions drawn from the literature search including the recommendations for HCVs.


2 Chemical overview Selenium (Se) is a metalloid element and its chemistry exhibits many similarities to that of sulphur.

The six stable isotopes of selenium are 74Se, 76Se, 77Se, 78Se, 80Se and 82Se. These isotopes occur naturally with approximate abundances of 0.87, 9.02, 7.58, 23.52, 49.82 and 9.19 per cent respectively (Hoffmann and King, 1997).

The -2, 0, +4 and +6 oxidation states are all commonly found in nature (IPCS, 1987), though other oxidation states (+1, +2, and the +3 cation Se4

12+) are possible for selenium. Elemental selenium can exist in several allotropic states. The grey or hexagonal form is stable at ordinary room temperature. The other important allotropes are red (monoclinic) selenium and amorphous selenium – the latter existing in red and black forms (ATSDR, 2003). Elemental selenium is not normally found in the natural environment, but is produced as a by-product of copper refining (IPCS, 1987).

Many organic compounds containing selenium have been identified in nature, with some having important metabolic roles (IPCS, 1987). Selenomethionine makes up a substantial proportion of selenium in cereals (SACN, 2006). The wide variation in levels of naturally occurring selenium in the environment has led to both deficiency and toxicity in humans and other animal species (IPCS, 1987).

The consumption pattern for selenium by US industry in 2002 was (ATSDR, 2003): glass manufacturing, 35%; chemicals and pigments, 20%; electronics, 12%; miscellaneous (including agriculture and metallurgy), 33%.

The glass industry uses selenium in the production of red and black glasses, and to counter the coloration from iron impurities. Important compounds in this context – and in the pigments of paints, plastics and inks – include sodium selenate (SeO4

2–) and sodium and ammonium selenite (SeO3

2–). The photoelectric and semiconductor properties of elemental selenium and cadmium selenide (CdSe) make them of value to the electronic and photocopying industries. Selenium also appears in rectifiers, photoelectric cells and in the coating on the metal cylinders that transfer the image in photocopiers. Selenium and selenium dioxide (SeO2) are valued as catalysts for the production of pharmaceutical and other organic compounds. Selenium sulphide (SeS) and disulphide (SeS2) are used as anti-dandruff ingredients in shampoos. Selenium compounds are also used as fungicides, nutritional additives for livestock and poultry, and as vulcanising agents for rubber (IPCS, 1987; ATSDR, 2003).

The major sources of selenium released into the environment include the burning of fossil fuels (particularly coal), the mining and refining of copper and other metals, and the manufacture of glass and electronic and photocopier components (IPCS, 1987).

The volatile selenium compounds that partition into the atmosphere include the inorganic compounds, selenium dioxide and hydrogen selenide, and the organic compounds, dimethyl selenide and dimethyl diselenide (ATSDR, 2003).

In soil, elemental selenium is essentially insoluble and may represent a major inert ‘sink’ for selenium introduced into the environment under anaerobic conditions (ATSDR, 2003). The main forms of selenium in soil are selenate (Se6+), selenite (Se4+), and selenide (Se2-), with the proportions in soil solution governed by various physical-chemical properties including pH and oxidation potential, and also biological processes (Kabata-Pendias and Mukherjee, 2007). Selenates occur under oxidising conditions and are very weakly adsorbed to soils at alkaline pH. Selenites occur under mildly reducing conditions and are readily sorbed on hydrous sesquioxides (such as aluminium oxide) and organic matter, or precipitated as iron complexes. In poorly


drained and acidic soils, immobile selenides are likely to form. Organic matter also has a strong tendency to form organic-metallic complexes which remove selenium from soil solution (Kabata-Pendias and Mukherjee, 2007). Because of their high solubility and low tendency to adsorb onto soil particles, the selenates are very mobile (ATSDR, 2003). Although selenites are usually soluble in water, in acid soils selenium is usually found as selenite bound to iron and aluminium oxides in compounds of very low solubility (WHO, 2003).

Elemental selenium and inorganic selenium compounds such as sodium selenite can be methylated by micro-organisms in soil, with subsequent volatilisation to the atmosphere (ATSDR, 2003). This transformation depends strongly on temperature and on the concentration and chemical form of the selenium, with elemental selenium being converted the most slowly and organic compounds the most rapidly – more than selenite or selenate (ATSDR, 2003).

The prevalence of selenium in the form of sulphides is expected to be low in the soil environment; selenium soil chemistry is dominated by selenates, selenites and selenides (Kabata-Pendia and Mukhejee, 2007), and texts on selenium soil chemistry (Neal, 1995; Kabata-Pendia and Mukhejee, 2007) do not include selenium sulphide. Information on selenium sulphides is included in this report for completeness, but the apparently different toxicity profile of selenium sulphide (notably the carcinogenic potential) to other forms of selenium means that the sulphides are not covered by the proposed HCV.


3 Toxicity

3.1 Literature sources This section is based largely on the many extensive published reviews that attempt a comprehensive view of selenium toxicity and metabolism, including those of:

• UK Expert group on Vitamins and Minerals (EVM, 2002, 2003) • World Health Organization (WHO, 1993, 1996) • International Programme on Chemical Safety (IPCS, 1987) • EU Scientific Committee on Food (SCF, 2000) • US Agency for Toxic Substances and Disease Registry (ATSDR, 1996, 2003) • US Environmental Protection Agency (USEPA, 1984, 1989, 1991, 1993a,

1993b) • and Harr and Muth (1972), Ganther (1987), Daniels (1996), and Foster and

Sumar (1997)

Particular mention is made of those studies used in deriving HCVs. In general, the primary references have not been consulted.

3.2 Pharmacokinetics

3.2.1 Absorption

Laboratory animal studies have indicated that selenium is extensively absorbed after inhalation exposure, with the rate being dependent on chemical form and particle size (ATSDR, 2003).

Oral studies with volunteers or rats have indicated from about 50% to total absorption of various selenium compounds (including sodium selenite, sodium selenate, selenomethionine and selenocysteine) given as solutions or in the diet. Although selenium compounds are generally readily absorbed from the human gastrointestinal tract, absorption can be affected by the physical state of the compounds (solid or solution) and the chemical form of selenium (e.g. inorganic, organic). In general, absorption appears to be independent of exposure level, although increased absorption may sometimes occur in subjects suffering from selenium deficiency (ATSDR, 2003). Evidence from rats suggests that absorption primarily takes place in the duodenum and, to a lesser extent, the jejunum and ileum (ATSDR, 2003).

Human studies of dermal absorption of selenium compounds (shampoos containing selenium sulphide or selenium disulphide, and a lotion containing selenomethionine) indicate that selenium is not taken up through human skin; however, the dose of selenomethionine tested was very low – 2.9 µg Se per kg bodyweight (µg Se kg-1 bw) – and it is possible that absorption may have taken place but was not detected (ATSDR, 2003). Dermal absorption of selenomethionine has been reported in mice (ATSDR, 2003).

In other rodent studies, 10–30% of the selenious acid applied to the skin of rats was absorbed (Medinsky et al., 1981), and 10% absorption of selenium was reported when


the tails of rats were in contact with a 0.1M solution (26 g L-1) of sodium selenite for one hour (Dutkiewicz et al., 1971).

3.2.2 Distribution and metabolism

Concentrations of selenium are slightly higher in the liver and kidney than in other tissues (EVM, 2003).

The metabolism of selenium results in its incorporation into a number of selenoproteins that include selenocysteine in their structure. Selenide is the important selenium species in the metabolic pathways for the formation and degradation of selenium proteins and it can be formed by reduction of selenite by glutathione in human (and rat) red blood cells (Lee et al., 1969; Gasiewicz and Smith, 1978).

The methylation of selenium is dose-dependent and the methylation pathway is an important detoxification route at high doses. Methylation produces the trimethyl selenonium ion, which is excreted via the kidneys (IPCS, 1987). When this pathway is overloaded, dimethylselenide is produced (IPCS, 1987).

3.2.3 Excretion

The main route of excretion of selenium in humans and other animals is in urine, with the trimethyl selenonium ion being a major urinary metabolite.

The garlic odour on the breath of over-exposed individuals is due to dimethylselenide (McConnell and Portman, 1952; Wilbur, 1980; Bopp et al., 1982), probably formed in the liver.

Faecal excretion also occurs, particularly after chronic exposure, and can occur to an equivalent extent to urinary excretion when exposures are not excessive (ATSDR, 2003; EVM, 2003).

3.3 Acute and subacute toxicity Acute selenium toxicity in humans is characterised by hypersalivation and emesis. These effects may be accompanied by further gastrointestinal effects (severe vomiting and diarrhoea), hair loss, neurological disturbance (restlessness, spasms, tachycardia) and fatigue (EVM, 2003). In humans, ingestion of single doses of 250 mg of selenium (or multiple doses of 27–31 mg) has resulted in overt signs of toxicity (nausea, vomiting, nail changes, dryness of hair, hair loss, tenderness and swelling of fingertips, fatigue, irritability and garlicky breath) (Jensen et al., 1984; SCF, 2000). A 15-year old female survived after ingesting a solution of sodium selenite estimated to have provided a dose of 22 mg Se kg-1 bw, probably because she was made to vomit soon after (Civil and McDonald, 1978).

Selenium exhibits a moderate to high acute toxicity in laboratory animal species, producing effects on the nervous system, liver and lungs (EVM, 2003). Oral LD50 values of 3.2, 4.8–7.0, 1.0 and 2.3 mg kg-1 bw have been reported for sodium selenite in mice, rats, rabbits and guinea pigs respectively (ATSDR, 2003). Elemental selenium is less toxic than most other selenium compounds, because of its very low solubility – an oral LD50 of 6,700 mg kg-1 bw has been reported in rats (Cummins and Kimura, 1971).


Very old acute inhalation studies in experimental animals report no deaths among rabbits or guinea pigs exposed to elemental selenium dust at 31 mg m-3 for four hours per day, every other day, for eight exposure days (Hall et al., 1951), though there were deaths in guinea pigs exposed to hydrogen selenide for two, four or eight hours at 6 and 12 mg Se m-3 (Dudley and Miller, 1941).

Rats exposed for one hour to approximately 26 g Se m-3 (25,958 mg Se m-3) as dimethyl selenide suffered only minor effects (transient increased lung and liver weight) (Al-Bayati et al., 1992). Dimethyl selenide thus appears to be relatively non-toxic by inhalation compared with hydrogen selenide (ATSDR, 2003); methylation is the primary detoxification route for selenium (see Section 3.2.2).

3.4 Subchronic and chronic toxicity The major study of selenium toxicity in humans arising from long-term exposure (to organic selenium) comes from China (Yang et al., 1983, 1989a, 1989b). Clinical signs of ‘selenosis’ (chronic selenium toxicity) included thickened and brittle nails, “garlic odour” on breath, sweat and urine, hair and nail loss, lowered haemoglobin, mottled teeth, skin lesions and neurological effects such as peripheral hypoaesthesia, acroparasthaesia, limb pain, hyperreflexia, numbness, convulsions and paralysis. The source of the selenium was a high selenium content coal, which weathered and leached into the soil. The local practice of liming the agricultural land made the selenium more available for plant uptake. The average daily intakes in the low-, medium- and high-selenium areas studied were 70, 195 and 1,438 µg day-1 for adult males.

A detailed examination of 349 adult residents correlated blood selenium levels with a clinical diagnosis of selenosis based on two grades of nail disease (Yang et al., 1989b). The more severe grade was found in six individuals and the milder symptoms were present in 54 cases. Selenium was found in individuals of all ages, but symptoms of selenosis were generally confined to adults (97%) and were never seen in children younger than 12. Blood selenium concentrations of five patients with ‘long-persisting, distinct clinical signs’ ranged from 1.054 to 1.854 mg L–1, and the lower end of this range corresponded to a daily selenium intake of 910 µg (Yang et al., 1989a). The investigators concluded that “an approximate marginal daily safe [selenium] intake of 750–850 µg day-1 is suggested from quantitative results of biochemical parameters”. According to the UK Expert Group on Vitamins and Minerals, the studies indicated that selenium intakes of 910 µg day-1 would produce mild signs of selenosis (EVM, 2003). The follow-up of five patients initially showing overt signs of selenosis found that their symptoms resolved after a change in diet that reduced selenium intake to 650–950 µg day-1 (Yang and Zhou, 1994).

The ‘no effect’ levels indicated by the Chinese studies are supported by findings from the northern part of the US Mid West (Longnecker et al., 1991). Almost 150 volunteers from an area of livestock selenosis were followed for one year. The range of intakes was estimated to be 68–724 µg day-1, with an average of 239 µg day-1, but there was no evidence of nail disease or any convincing indication of other adverse effects.

Signs of selenosis were similarly absent in Venezuelan lactating mothers with dietary intakes in the region of 500 µg Se day-1 (Brätter and Negreti de Brätter, 1996). Children living in a seleniferous area of Venezuela exhibited more pathological nail changes, hair loss and dermatitis than children from the capital Caracas. Their estimated daily intake of selenium, based on the relationship between blood levels and intake seen in the Chinese study, was 660 µg (Jaffe, 1976).


There were signs of very mild (and subclinical) effects on the thyroid hormones in the Venezuelan population with high selenium intake (Brätter and Negreti de Brätter, 1996). Similar effects were seen in a 120-day double-blind study in 11 US volunteers (Hawkes and Turek, 2001; Hawkes et al., 2001). After 21 days on a diet providing 47 µg day-1 of selenium, six of the men were fed a diet delivering 13 µg day-1 for the remaining 99 days, with the other five men receiving 297 µg day-1. As well as the slight changes in thyroid hormone level seen in the high selenium subjects, there was some indication of a reduced sperm motility (although again the values remained within the normal range), and a mild and transient enhancement of the immune system.

A number of other studies have reported on the health of volunteers taking selenium supplements (Tarp et al., 1985; Meltzer, 1995; Clark et al., 1996) or bread made with selenium-enriched wheat (van Dokkum et al., 1992). No signs of selenium-related toxicity were recorded in these test subjects, who would have been receiving doses in the range 200–400 µg day-1. In the investigation by Clark et al. (1996), a large group of US volunteers were estimated to have had total selenium intakes of about 200 µg day-1 for up to 10 years.

The interpretation of laboratory animal studies of selenium toxicity from repeated oral administration is complicated by the many variables involved, including the form of the administered selenium and the type of diet.

3.5 Reproductive and developmental toxicity Reproductive toxicity was not examined in detail in the available epidemiological studies (EVM 2003).

Fertility was reduced in rats and mice exposed to selenium at levels sufficient to produce general toxicity. Selenium deficiency has also been shown to reduce sperm production in rats. There is no evidence from studies in experimental animals treated either orally or by injection that selenium compounds are able to induce foetal abnormalities at doses below those causing overt toxicity to the mothers (ATSDR, 1996). Teratogenicity has been described in hamsters, sheep and pigs at maternally toxic doses (SCF, 2000; EVM, 2003).

3.6 Genotoxicity Sodium selenite and selenate have produced evidence of mutagenicity in Salmonella typhimurium (in Ames tests) and each induced unscheduled DNA synthesis and chromosomal damage in mammalian cells in culture (ATSDR, 2003).

In vivo tests have given both positive and negative results. There was no evidence of any treatment-related chromosome damage in the blood cells of five volunteers given 25 µg kg-1 bw day-1 of sodium selenite orally for two weeks, or of nine neuronal ceroid lipofuscinosis (a neurodegenerative disease) patients given 5–50 µg kg-1 bw day-1 for 1–13.5 months (Norppa et al., 1980a).

L-Selenomethionine administered by oral gavage at 240 µg Se kg-1 bw day-1 for 15 days (an overtly toxic dose) produced chromosome damage (micronuclei) in the bone marrow of monkeys (Choy et al., 1989). No increases in micronuclei in the bone marrow were detected in monkeys treated similarly at a dose of 120 µg Se kg-1 bw day-1 for 19 days, or in the offspring of monkeys given this dose on gestation days 20 to 50 (Choy et al., 1993), despite still causing observable signs of toxicity.


Chromosome breaks were seen in bone marrow cells of male mice after single oral doses of sodium selenite or sodium selenate (Biswas et al., 1997, 1999a; doses not specified in ATSDR, 2003). The administration of selenium sulphide by gavage to male rats at 12.5 mg kg-1 bw day-1 resulted in small increases in the level of chromosomal damage in the bone marrow in the form of micronuclei (Moore et al., 1996).

Chromosomal aberrations and increased sister chromatid exchange were seen in the bone marrow of hamsters given sodium selenite by intraperitoneal injection at 3, 4 and 6 mg Se kg-1 bw. These doses caused severe systemic toxicity including death. Lower doses of 0.3, 0.6, 1 and 2 mg Se kg-1 bw did not produce clastogenic effects (Norppa et al., 1980b).

Overall, the in vivo data are largely negative (EVM, 2003), except where there is overt toxicity.

Low level supplementation with selenium can have a protective effect against genotoxicity, while higher levels have shown themselves to be genotoxic. In vitro studies support the idea that selenium salts give rise to genotoxicity by the production of reactive oxygen radicals and that glutathione promotes these reactions (Kramer and Ames 1988). It has been suggested that metabolites such as hydrogen selenide are central to this redox cycling action, and that this will only become significant once methylation detoxication becomes saturated. Thus, the genotoxic effect of selenium is likely to demonstrate a threshold (SCF, 2000).

3.7 Carcinogenicity A working group of the International Agency for Research on Cancer concluded in 1975 that the laboratory animal data on selenium compounds were insufficient or inadequate to allow any evaluation of their carcinogenic potential (IARC, 1975).

In 1993, the US Environmental Protection Agency recorded a similar view (“not classifiable as to carcinogenicity in humans” – Group D) for “selenium and compounds” 2 (USEPA, 1993a). In contrast, USEPA classified selenium sulphide and disulphide as “probable human carcinogen[s]” (Group B2) (USEPA, 1993b) on the basis of laboratory animal studies.

In 2003, the US Agency for Toxic Substances and Disease Registry added to the opinion that the sulphides were the only selenium compounds to have clearly exhibited a carcinogenic potential (ATSDR, 2003), but noted that selenium sulphide “is very different from the organic and inorganic selenium compounds found in foods and in the environment”.

A mixture of selenium sulphide and selenium disulphide, administered by gavage for 103 weeks, produced liver cancer both in rats and mice (NTP 1980a). In the rats, the liver tumours were found only in the high-dose group (which received daily doses of 15 mg kg-1 bw); none were found in the 50 males and 50 females of either the untreated control group or the group given 3 mg kg-1 bw day-1. In the female mice, there was a high incidence of liver cancers in the top dose group of 100 mg kg-1 bw day-1, and a low incidence at 20 mg kg-1 bw day-1. Again, tumours were not found in the 50 controls. Although the pattern of the data was not as conclusive, signs of liver carcinogenicity were also seen in the male mice. Lung tumours were also found in the mice. It was not possible to ascribe the tumours in the males to treatment as

2 The carcinogenicity assessment was said to apply to selenium (CASRN 7782- 49-2), sodium selenate (CASRN 13410-01-0), sodium selenite (CASRN 10102-18-8), selenious acid (CASRN 7783-00-8), selenic acid (CASRN 7783-08-6), and sodium selenide (CASRN 1313-85-5).


incidences were within the high background control range; however, in the females, which have a lower spontaneous background rate, there was a treatment-related increase in incidence.

The dermal application of the same sulphide mixture (NTP 1980b) or of a commercial preparation of 2.5% selenium sulphide (NTP 1980c) to Swiss mice for 86 weeks produced no conclusive evidence of carcinogenicity. A slightly raised incidence of lung tumours was found in the male mice treated with the commercial preparation. The maximum tested doses were of the order of 30–50 mg kg-1 bw per application, and the mice were treated three times per week.

3.8 Summary Single oral doses of 250 mg or multiple doses of 27–31 mg selenium have produced overt signs of toxicity in humans, including gastrointestinal effects and neurological disturbances.

Long-term repeated ingestion of selenium in food has resulted in a range of adverse effects in humans. Selenosis is characterised by changes to the hair and nails, skin lesions and clinical neurological effects (e.g. peripheral hypoaesthesia, acroparasthesia, pain, hyperreflexia and numbness). Convulsions and paralysis may develop. Daily doses of 910 µg have produced the milder signs of selenosis in Chinese adults.

The developmental and reproductive toxicity that resulted from the administration of selenium compounds to laboratory animals occurred at doses that were also toxic to the parental generation.

In general, only limited carcinogenicity studies have been reported on selenium compounds. With the exception of selenium sulphides, these have not given convincing evidence of carcinogenicity. Higher quality oral studies have been conducted on a mixture of selenium sulphides in rats and mice and there was clear evidence of liver carcinogenicity in both species and also evidence of lung carcinogenicity in mice.

Some selenium compounds have given indications of genotoxic effects when administered orally to laboratory animals. However, there is evidence that selenium compounds have given rise to genotoxicity by the production of reactive oxygen species; thus, it has been concluded that the genotoxic effect of selenium is likely to have a threshold (SCF, 2000).


4 Essentiality and deficiency Selenium is important for an extensive range of biochemical functions within the body. These functions are mediated by at least 20 selenoproteins, such as glutathione peroxidase (GSHPx), which contain selenocysteine at their active site. These proteins play a key role in a number of metabolic processes including antioxidant systems, thyroid hormone metabolism, immune function and reproduction (SCAN, 2006). The latest World Health Organization (WHO) recommendations on the levels of oral intake of selenium necessary for the maintenance of good health are 33–34 µg day-1 for adult males and 25–26 µg day-1 for adult females (35–42 µg day-1 for lactating women) (WHO, 2004).

Selenium deficiency has been strongly associated with two widely endemic diseases in China: Keshan disease, a cardiomyopathy; and Kashin-Beck disease, a chronic osteoarthropathy (IPCS, 1987; CAS, 1989; Jian’an et al., 1990). These conditions have been associated with large areas of selenium deficiency in the soils, and corresponding animal conditions such as white muscle disease. Both diseases primarily affect children and women of child-bearing age, though the age distribution is markedly different in different areas of the country. The aetiology is complex, with other factors such as nutritional status, living standards, viruses and high phosphate and manganese content of soils being implicated; however, selenium supplementation has been shown to be of great preventative and therapeutic value. This has been achieved by administering sodium selenite either by direct injection, or by addition to table salt or onto soils to increase the selenium content of grain.

It has been reported that 25% of apparently healthy volunteers in a selenium-deficient area of north-west England had serum selenium less than that required for “full expression of selenium dependent enzyme activity” (Pearson et al., 1990). However, WHO (2004) has noted that “it is neither essential nor desirable to maintain selenium status at a level which fully saturates blood GSHPx activity when, based on current evidence, this is not an advantage for health”.

Biochemical evidence of selenium deficiency is seen in subjects maintained on parenteral or enteral feeding for long periods, but clinical effects are uncommon and poorly defined, though may include muscular weakness and myalgia, with “in several instances, the development of congestive heart failure” (WHO, 2004).

There is no confident understanding of the impact (if any) of selenium status on susceptibility to viral diseases (WHO, 2004). Beneficial effects of selenium intake on Acquired Immune Deficiency Syndrome (AIDS) symptoms, male fertility, skin disorders, anxiety, heart disease, thyroid problems and asthma have also been claimed (EVM, 2003; WHO, 2004), but again empirical support is currently inadequate.

The possibility that increased intakes of selenium might protect against the development of a range of cancers in humans is much discussed. As yet, there is not widespread confident support for these possible anti-cancer benefits from expert groups (DH, 1998; WHO, 2004; NIH, 2006), but a 2007 review by the World Cancer Research Fund concluded that selenium-containing foods (whether naturally containing selenium or having had it added) are probably protective for prostate cancer and there is suggestive evidence for lung, stomach, and colorectal cancers also (WCRF, 2007).


5 Derivation of Health Criteria Values

5.1 UK Expert Group on Vitamins and Minerals The UK Expert Group on Vitamins and Minerals (EVM) was established in 1998 to advise on safe levels of intakes of vitamins and minerals in food supplements and fortified foods. Its resulting report was published in May 2003 (EVM, 2003).

A Safe Upper Level3 of 450 µg of total selenium (“ionic selenium”) per day was established.4 This was derived from the lowest-observed adverse effect level (LOAEL) of 910 µg Se day-1 for mild signs of selenosis (changes in the hair and nails) indicated in an exposed Chinese population (Yang et al., 1989a, 1989b) and the use of an uncertainty factor (UF) of 2 to convert the LOAEL for “slight effects” to a NOAEL (no-observed adverse effect level). As the LOAEL was from a population study, a UF to take into account interindividual variation was said not to be required. A maximum intake of 100 µg day-1 of selenium from food was assumed, leaving a margin of 350 µg day-1 “available for supplementation or other additional intake” (EVM, 2003).

5.2 UK Committee on the Medical Aspects of Food and Nutrition Policy

The study of Yang et al. (1989b), providing evidence of “disturbed [selenium] homeostasis” at intakes above 750 µg day-1 and early effects on the nails at 900 µg day-1, was accepted by the Panel on Dietary Reference Values of the UK Committee on Medical Aspects of Food Policy as being critical in providing “guidance on high intakes” (DH, 1991). “Given the absence of any demonstrable benefit from exceeding intakes much lower than these [the Panel recommended] that the maximum safe [selenium] intake from all sources should be 450 µg day-1 for adult males, corresponding to 6 µg kg-1 bw day-1”.

5.3 EU Scientific Committee on Food On the basis of the Chinese findings (Yang et al., 1989b), the EU Scientific Committee on Food (SCF) noted that an intake of about 850 µg day-1 “could be taken as a NOAEL for clinical selenosis”. Although it was acknowledged that this NOAEL was generated from a study on a large number of subjects that would be expected to include sensitive individuals, it was “decided to use an UF of 3 to allow for the remaining uncertainties of the studies used in deriving an upper level”. The application of this UF (and rounding)

3 A Safe Upper Level (SUL) represents an intake that can be consumed daily over a lifetime without significant risk to health on the basis of available evidence. 4 EVM, either in error or by rounding, equated the 450 µg day-1 to 5 µg kg-1 bw day-1 for a 60 kg adult, whereas it should have been 7.5 µg kg-1 bw day-1 based on a bodyweight of 60 kg – the 7.5 µg kg-1 bw day-1 value was cited in two reports by the Committee on Toxicity in 2003 (COT, 2003a). Based on a bodyweight of 70 kg, it would equate to 6.4 µg kg-1 bw day-1.


generated a tolerable upper intake level (UL)5 of 300 µg day-1 of selenium for a 60 kg adult or 5 µg kg-1 bw day-1 (SCF, 2000).

The follow-up study of Yang and Zhou (1994), the supplement study of Clark et al. (1996), the American study of Longnecker et al. (1991) and a study of lactating Venezuelan women (Brätter and Negreti de Brätter, 1996) were said to offer further support for this UL. The UL was to cover “selenium naturally present in food” as well as sodium selenate, sodium selenite and sodium hydrogen selenite. It was said to be applicable to pregnant and lactating women, and, after account had been taken of differences in bodyweight, to children.

5.4 European Food Safety Authority The Scientific Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) of the European Food Safety Authority (EFSA) reported in December 2006 on an evaluation of a product (Alkosel®) that was intended to be used in all farm animal species as a source of selenium. Selenium is present in Alkosel® in an organically bound form (mainly selenomethionine). Assessment of consumer safety – which assumed the ingestion of edible tissues and products from animals fed the maximum permitted levels of the supplement in feed, and took account of background intake of selenium – was based on the UL of 300 µg day-1 recommended by SCF in 2000. The FEEDAP Panel was “not aware of more recent data that may modify the opinion of the SCF”. It was concluded that the intakes of selenium from the consumption of food commodities from Alkosel®-treated animals was unlikely to exceed the recommended overall UL (and its equivalent for various age groups) (FEEDAP, 2006a).

An earlier FEEDAP evaluation of another selenium feed additive (Sel-Plex® – again mainly selenomethionine) had led to the same conclusion (FEEDAP, 2006b).

5.5 World Health Organization In an early 1990s derivation of a health-based guideline value for selenium in drinking-water, a World Health Organization (WHO) Task Group concluded that the estimated NOAEL in humans was about 4 µg kg-1 bw day-1, on the assumption that soluble selenium salts in drinking-water may be more toxic than organic-bound selenium in food (WHO, 1993, 1996). This NOAEL took account of the reports of Yang et al. (1989a, 1989b) and Longnecker et al. (1991) as well as studies of Venezuelan children (Jaffe, 1976) and patients taking supplements of selenium-enriched yeast (Tarp et al., 1985).

A WHO Final Task Force meeting in 2003 agreed that this earlier risk assessment was still valid. It was thus brought forward to be included in a 2006 revision of the drinking-water guidelines (WHO, 2006). Based on a 60-kg adult drinking two litres of water per day, and allocating 10% of the NOAEL to exposure from drinking-water, the WHO guideline was 10 µg L-1.

5 A tolerable upper level (UL) is the maximum level of total chronic daily intake of a nutrient (from all sources) judged to be unlikely to pose a risk of adverse health effects to humans.


5.6 US Environmental Protection Agency The US Environmental Protection Agency (USEPA) considered the study of Yang et al. (1989b) to be critical in its 1991 derivation of an oral Reference Dose (RfD)6 for ”selenium and its compounds”.7 It involved a large sample size and included analysis of tissue selenium levels that allowed an estimation of the dose–response of selenium toxicity. The NOAEL of “853 µg selenium/day” was corroborated by a study of US volunteers (Longnecker et al., 1991). An UF of 3 to ensure protection of the most susceptible individuals and a bodyweight of 55 kg (the Yang study was of Chinese peasants) produced, after rounding, an RfD of 5 µg kg-1 bw day-1. The default UF of 10 for intra-individual variation “was not deemed necessary since similar NOAELs were identified in two moderately-sized human populations [Yang et al., 1989b; Longnecker et al., 1991] exposed to selenium in excess of the recommended dietary allowance throughout a lifetime without apparent clinical signs of selenosis” (USEPA, 1991).

5.7 US Agency for Toxic Substances and Disease Registry

The US Agency for Toxic Substances and Disease Registry (ATSDR, 2003) based its Minimal Risk Level (MRL)8 for chronic oral exposure to selenium on the Chinese experiences (Yang et al., 1989a, 1989b; Yang and Zhou, 1994). Using a regression equation linking blood selenium concentration to dietary intakes derived from the findings in the wider population (Yang et al., 1989b), the findings of the study of the five individuals whose symptoms resolved when they ingested lower dietary concentrations of selenium (Yang and Zhou, 1994) was said to show a mean NOAEL of 819 µg day-1 (equivalent to 15 µg kg-1 bw day-1 for the 55-kg subjects) and a mean LOAEL of 1,270 µg day-1 (23 µg kg-1 bw day-1) for the initial signs of selenosis (nail disease). An UF of 3 for human variability (a reduced value from the default 10 because the subjects were sensitive individuals drawn from the larger population) was applied to the NOAEL to produce a chronic oral MRL of 5 µg kg-1 bw day-1.

5.8 Discussion There is unanimity among the expert groups that the heavily exposed population within mainland China offers the best opportunity of defining the toxicological consequences of long-term oral exposure to ‘selenium’ – a term which would appear to include all selenium compounds other than the sulphides.

On the basis of the findings of an exposed group of about 350 adults described by Yang et al. (1989b), USEPA in 1991 and SCF in 2000 agreed that the NOAEL for selenosis was about 850 µg day-1. Although ATSDR in 2003 based its determination of 6 An oral Reference Dose (RfD) is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious, non-cancer, effects during a lifetime. 7 The selenium compounds the RfD applied to were not defined specifically but from their appearance in the accompanying USEPA description of the selenium toxicity database would have included sodium selenite, sodium selenate, selenomethionine and selenoglutathione, which were said to be “among the more toxic species [of selenium compound]”.

8 An ATSDR Minimal Risk Level (MRL) is an estimate of daily human exposure to a hazardous substance at or below which it is unlikely to cause a measurable risk of harmful non-cancerous effects. MRLs are derived for a specified route and duration of exposure.


the NOAEL on a later “reversibility” study (Yang and Zhou, 1994) which involved only five of the more heavily exposed individuals within the larger group, the derived value (819 µg day-1) was essentially the same.

There was also agreement between ATSDR and USEPA over the use of an UF of 3 to take account of the interindividual variations in sensitivities to selenium toxicity that might not have been faithfully reflected in their chosen critical studies. In the light of the unusually large group size of Yang and co-workers, SCF felt that no UF for interindividual variations was necessary, but brought an UF of 3 into its own derivation to insure against any remaining uncertainties in the critical study. There were slight differences too between the conversions of the per capita NOAEL to its µg kg-1 bw equivalent, in that the 55-kg average bodyweight of the exposed Chinese population was used by USEPA and ATSDR, whereas SCF favoured a standard default bodyweight of 60 kg. Nevertheless, the three derivations resulted in the same oral health criteria value of 5 µg kg-1 bw day-1 once rounded.

The most recent UK determination of a tolerable oral dose of selenium was that of EVM. Although also using the findings of Yang et al. (1989b), EVM preferred the starting point to be an estimated LOAEL for mild toxicity of 910 µg day-1. Like SCF, it felt that no UF for interindividual variation was necessary (as the examined exposed group was assumed to have included all sensitivities), but an UF of 2 was invoked to convert the minimal LOAEL to a NOAEL. The resulting Safe Upper Level was 450 µg day-1.

No expert group derivations of health criteria values for the inhalation of selenium were identified.


6 Background intake

6.1 Food The latest estimates of the dietary exposures of the UK population to selenium – a mean daily intake (MDI) of 34 µg day-1 – came from the 2000 UK Total Diet Study (COT, 2003a). Intakes have declined steadily from about 60 µg day-1 in the mid-1970s and 1980s (Ysart et al., 2000). A 2001–2002 UK survey of the metal content of infant foods indicated a mean intake of selenium by infants of 0.43 µg kg-1 bw day-1, compared with an intake of 0.54 µg kg-1 bw day-1 seen in the previous equivalent exercise reported in 1999 (COT, 2003b).

6.2 Water WHO (1987, 1996) reported that concentrations of selenium in water supplies are usually much less than 10 µg L-1. One survey in the USA found only 3.3% of surface water samples to have a selenium level above 1 µg L-1 (ATSDR 1996).

A summary of the regulatory compliance data for 2004–2007 submitted to the Drinking Water Inspectorate (DWI) by each of the water companies in England and Wales is provided in Table 6.1. Where results were less than the limit of detection (LOD) – which is variable between water suppliers but typically around 0.2 µg L-1 for selenium – they have been assumed to be at the LOD; thus the results in Table 6.1 represent worst-case values (Marsden, 2008).

Based on the DWI data, the MDI of selenium from drinking-water is assumed to be around 1 µg day-1.

Table 6.1 2004–2007 regulatory drinking-water compliance data for selenium in England and Wales (Marsden, 2008)

Concentration (µg L-1) Year No. samples taken

No. samples above PCVa

Min Mean Max 97.5%ile

2004 12,616 0 0.01 0.89 9.06 3.30

2005 12,694 0 0.01 0.85 8.30 3.00

2006 12,677 0 0.01 0.78 7.80 3.10

2007 12,579 1 0.01 0.65 10.20 1.90 a The Prescribed Concentration or Value (PCV) for selenium is 10 µg L-1.

6.3 Air Mean aerial concentrations of selenium of 0.9–3.0 ng m-3 have been reported at a number of UK rural, residential and urban sites, with a mean concentration of 16.7 ng m-3 at an industrial area (Lee et al., 1994). Selenium concentrations of up to 4 ng m-3 have been found at a rural grassland site in the UK (Haygarth et al., 1994).


6.4 Other sources Selenium is present in some licensed medicines and a variety of food supplements. These may provide daily doses of up to 300 µg (EVM, 2003). In estimating MDI values, no account has been taken of the intake of selenium from medicinal or food supplement products.

6.5 Estimation of mean daily intakes The adult oral mean daily intake (MDIoral) for selenium from food (34 µg day-1) and water (1 µg day-1) combined is estimated to be 35 µg day-1.

Based on an assumed average ambient selenium concentration of 3 ng m-3 and the default adult inhalation rate of 20 m3 of air per day (Environment Agency, 2009a), the adult inhalation mean daily intake (MDIinh) is 0.06 µg day-1.


7 Conclusions Adverse effects on human health occur both from too much and from too little exposure to selenium. WHO recommends minimum selenium oral intakes of 33–34 µg day-1 for adult males and 25–26 µg day-1 for adult females (35–42 µg day-1 for lactating females), while the milder features of selenosis (from too much selenium) are thought to occur at daily oral doses in adults of about 910 µg.

The UK Expert Group on Vitamins and Minerals has estimated that a daily oral dose of 450 µg of selenium would not pose a significant risk to the health of an adult. Based on the default adult bodyweight of 70 kg, this is equivalent to 6.4 µg kg-1 bw day-1, which is recommended here as the TDIoral. The milder signs of selenosis (involving changes to the nails and hair) might be expected to develop at exposures as low as twice this, i.e. at around 13 µg kg-1 bw day-1.

The proven liver carcinogenicity in rodents of selenium sulphides means that the TDIoral is not applicable to selenium in the form of sulphides, but these are not anticipated to be prevalent in the soil environment.

There are no expert group evaluations of inhalation or dermal exposure to selenium, and data for these routes appear very limited. Use of route-to-route extrapolation to propose a TDIinh based on the TDIoral is complicated by the variety of forms in which selenium may present and the lack of available comparable data on kinetics or toxicity between routes. The limited information on absorption that is available indicates that selenium is extensively absorbed following both oral and inhalation exposure, but the limited toxicity data suggest that local respiratory toxicity could be important for at least some forms of selenium. In view of the uncertainties around inhalation toxicity, and since oral exposure would be expected to dominate a risk assessment of selenium in soil (Environment Agency, 2009b), no TDIinh is proposed here. It is nonetheless preferable to still account for inhalation exposure in the overall risk assessment of selenium. This may be achieved rudimentarily by comparing the inhalation exposure against the TDIoral.

The adult MDIoral is estimated to be 35 µg day-1; the adult MDIinh is estimated to be 0.06 µg day-1 (see Table 7.1).

Table 7.1 HCV and MDI values for selenium

Parameter Oral Inhalation

MDI (µg day-1) 35 0.06

MDI for 70 kg adult (µg kg-1 bw day-1) 0.5 0.0009

MDI for 20 kg child (µg kg-1 bw day-1) 1.3 a 0.002 a

TDI (µg kg-1 bw day-1) 6.4 Not derived a see Environment Agency (2009a) for details of MDI conversion factors.


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List of abbreviations ATSDR Agency for Toxic Substances and Disease Registry [USA]

bw bodyweight

COT Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment [UK]

Defra Department for Environment, Food and Rural Affairs [UK]

DH Department of Health [UK]

DWI Drinking Water Inspectorate [UK]

EFSA European Food Safety Authority

EVM Expert Group on Vitamins and Minerals [UK]

FEEDAP Panel on Additives and Products or Substances used in Animal Feed [EFSA]

GSHPx glutathione peroxidase

HCV health criteria value

IPCS International Programme on Chemical Safety

LOAEL lowest-observed adverse effect level

LOD limit of detection

MDI mean daily intake

MRL minimal risk level

NIH National Institutes of Health [USA]

NOAEL no-observed adverse effect level

NTP National Toxicology Program [USA]

PCV Prescribed Concentration or Value

RfD Reference Dose

SACN Scientific Advisory Committee on Nutrition [UK]

SCF Scientific Committee on Food [EU]

SUL Safe Upper Level

TDI tolerable daily intake

UF uncertainty factor

UL upper intake level

USEPA US Environmental Protection Agency

WCRF World Cancer Research Fund


Appendix – Literature search The literature search that formed the basis of this update report was undertaken using a proprietary database – the TRACE database developed and managed by bibra toxicology advice & consulting. The database was searched in February 2007 for comprehensive reviews and evaluations of selenium. A search for primary literature published since the most recent expert group evaluation was later conducted in October 2008.

TRACE includes information from peer-reviewed toxicology and nutrition journals as well as secondary sources (websites, official publications and evaluations by authoritative groups) including:

• UK government agency (Defra and the Environment Agency, FSA, HPA) and advisory committee (COT, COM, COC, ACAF, ACNFP and ACP) reports and evaluations

• EU Risk Assessment Reports • EU expert committees (EU scientific committees, EFSA scientific panels) • WHO/IPCS reports and evaluations (including CICADs and EHCs, and IARC,

JECFA and JMPR monographs), and the WHO Air Quality and Drinking-Water Quality Guidelines

• US government agency reports and evaluations (EPA, ATSDR, FDA, NTP, OSHA, NCEA, CFSAN, CERHR, NIEHS and OEHHA)

• OECD SIDS dossiers/SIARS • ECETOC, ACGIH, BG Chemie and DFG reports and monographs • IUCLID data sets • NICNAS Priority Existing Chemical Assessments

land contamination: technical guidance - gov.uk

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