Medical

IS

THE

Michael Health,

Hypotheses

SELENIUM G. Lafond University

5: 877-899,

DRINKING and of

1979

WATER Edward J. Massachusetts,

STANDARD

JUSTIFIED?

Calabrese, Amherst,

Division MA

of 01003

Public

ABSTRACT Four cases are presented which suggest that the present U.S.E.P.A. drinking water standard for selenium of 10 ug/L i s inappropriate. The rationale upon which this standard is based is that selenium is carcinogenic, induces dental caries However, a critical format ion, and is highly toxic to animals. assessment of this literature can not support these claims. Case #l demonstrates that there is insufficient evidence to Data derived from the three classify selenium as a carcinogen. respective groups of researchers claiming a carcinogenic effect induced by selenium are obscure due to 1) the inability to accurately identify malignancies, 2) the apparent opposite effects of different selenium compounds, and 3) the lack of Case #2 reviews recent evidence that selenium proper controls. reduces the inoidence of cancer in laboratory animals and in man, an effect which can probably be attributed to the antiCase #3 provides oxidant properties of selenium compounds. evidence which does not permit the classification of selenium Epidemiological studies supporting as a cariogenic element. such a claim are inadequate since they lack properly matched control groups. Animal data do not support this link as Case #4 is a review of studies which clearly demonstrate we1 1. an aspect of selenium metabolism the essentiality of selenium, that was not considered when the 10 ug/L standard was promulgated. In light of the four cases presented and an assesment of selenium toxicity in man, it is concluded that the 10 ug/L Instead, it is suggested that standard can not be justified. 50 ug/L selenium should provide sufficient protection from the toxic effects of this element. This is consistent with the current state of knowledge with respect to the potential adverse health effects associated with selenium. Key

Words:

selenium,

cancer,

drinking

877

water,

standards,

diet

INTRODUCTION Public Health Service promulgated In 1942, the U.S. standard for selenium (50 ug/L). their first drinking water This standard only covered drinking water serving interstate the USPHS lowered this drinking water carriers. tn 1962, Furthermore, in the 1977 standard from 50 ug/L to 10 ug/L. ammendments to The Safe Drinking Water Act of 1974, the EPA retained the 1962 USPHS standard for selenium (10 ug/L) based on the same rationale (1). The information used to set the current selenium standard was quite limited and not especially recent. 10 ug/L standard was based on evidence which suggested that selenium is a carcinogen (2,3), 2) that selenium toxic to cattle (4) and fish (s), and 3) a possible epidemiological link between high selenium intake and creased rates of dental caries (6).

The 1) is in-

It is the intention of this paper to demonstrate that the evidence used by the USPHS and the EPA in setting the 10 ug/L drinking water standard is partially inaccurate and misleading. A review of the data used by these agencies and a review of more recent information indicates that there is no compelling evidence to suggest that selenium is a carcinogen. it has been suggested that selenium In fact, protects against cancer, both in laboratory animals and in man as demonstrated in epidemiological studies. In addition, selenium may not be as closely linked to dental caries as previous data may have suggested due to confounding variables in these epidemiological studies. In setting the standard, both agencies failed to take into account the essentiality of selenium in the human diet. Case --

#l:

-Is

Selenium

-a

carcinogen?

The carcinogenic potential of selenium has been claimed but challanged by others, based on by a few researchers, their own work or previous evidence. Among the earliest studies supporting a carcinogenic relationship is the study by Nelson et al (2). In their study, seven groups of 18 rats each were tested for selenium effects. The element was fed to the animals as seleniferous wheat or corn in six of the seven treatment groups, and as ammonium potassium selenide in the seventh treatment group. Levels of selenium and 10 ppm in the wheat and corn fed groups, and were 5,7, 10 ppm in the inorganic selenium fed group. Forty five out of within the first three due to the toxic effects two year study period, ment groups had died.

126 rats in the selenium groups died months of the experiment, presumably of selenium. By the end of the all but 39 of 126 rats in the treatindicated that the results Scott (7) 878

of this experiment can not be explained solely as selenium related effects. Differential mortality rates were noted between rats receiving seleniferous feed and rats given supplemental selenium. In fact, the data indicate that in the three IO ppm groups, 27 out of 54 animals died in the first three months. Of these 27 dead animals, 13 had been fed seleniferous corn (72% mortality), 12 were given seleniferous wheat (67% mortality), but only 2 received the supplemental selenide additive (119 mortality). A significant criticism of this study which casts doubt on the claim that selenium is carcinogenic was the difficulty that the researchers encountered in distinguishing between hyperplasia and true carcinomas. They noted that “The differentiation between adenoma and low grade carcinoma was difficult to make in this series of tumors...and anyone who has studied a series of the latter tumors will appreciate the difficulty of deciding just when the borderline between nonmalignant and malignant tumor has been passed, and also just when hyperplasia has passed into tumor”. However, Shapiro (8) indicated that these changes may have represented one phase of hepatic regeneration rather than neoplasia. It “tumors” to metastasize is noted that the inability of these implied a lack of malignancy. A group of Soviet researchers also claimed that selenium induced hepatic tumors. In their first report reviewed by Scott (7)) they noted that 10 out of 23 male rats fed 4.3 ppm selenium developed tumors, while 5 out of 13 rats given 6.6 ppm selenium showed cancerous growths. However, since the researchers failed to mention any controls, no definite conclusions can be made. In their second report (9) these same researchers were not able to support their prior claim. They noted that in two separate series of experiments, 5 out of 60 rats given selenium as selenate developed tumors in one series and 0 out of 100 rats on the same selenium treatin the second series. However, it ment developed tumors was noted that the normal spontaneous cancer rate for the strain of rats used was . 5% and it was this rate that was used as a basis for comparison with the selenate treated Because of this lack of proper controls, only suggestive rats. conclusions can be drawn from this report as well. also reported the potential Schroeder and Mitchener (10) carcinogenicity of selenium. 418 Long-Evans rats were and then were further divided by divided into four groups, sex. At the onset of the experiment, the groups included male 2 ppm selenate (males and females), 2 and female controls, ppm selenite (males and females), and 2 ppm tellurite (males the initial high die-off rate among and females). However, the selenite treated males (50% mortality at 58 days) compelled the researchers to substitute selenate for selenite in this After 12 months, the researchers raised the group only. selenate (males and females) and selenite (females) treatments from 2 ppm to 3 porn for the experiment. !Jh e n the rats were 21 months

879

Even old, a virulent pneumonia struck the colony of rats. though it was brought under control with penicillin after 3 weeks, losses were immense: 36% male controls, 49% selenate males, 37% tellurite males, 37% female controls, and 24% tellurite females were lost. 154 selenate females, With such a magnitude of losses, speculation must be made into the validity of using this surviving group without None the less, Schroeder and creating a statistical bias. The Mitchener continued their study using the survivors. following incidence of tumors was reported: 31% controls, 628 selenate, 12% selenite (females), and 36% tellurite. From these results, the researchers concluded that selenium was carcinogenic. In light of the extreme and highly differential die-off rate amongst the different exposure groups due to the pneumonia and the apparent opposite effects of selenate and selenite on the tumor incidence, it would seem that a much more cautious and restrained conclusion would be warranted. Unlike the earlier studies in which rates of hepatic Schroeder and Mi tchener’s study cancer were reported (2, 7,9), concluded that selenium predominantly induced mammary and subcutaneous fibrous cancers and not hepatic carcinomas. A was that despite the fact that Schroede point noted by Scott (7) and Mitchener stressed the importance of age as a contributing factor in the development of cancer, they failed to take 50% mortal i ty this into account in their own experiment. was observed at 962 days in selenate fed male rats and at However, 50% 1014 days in females on the same treatment. mortality in the controls occurred much earlier at only Thus, “it 853 days in males and 872 days in females. incongruous to point to a substance as a carcinogen appears because more individuals in the longer living group died of cancer” (7). It is well known that age is a contributing factor in the development of cancer, older animals being more susceptible. Consequently , one would expect that the older, longer lived selenate group should have more cancers. In essence, Schroeder and Mitchener’s results are of questionable validity because they failed to age-adjust. Interestingly, in a subsequent study, Schroeder and Mitchener (11) evaluated the effects of selenate and selenite on Swiss mice. They reported that these selenium compounds (i.e. selenate and selenite) were ineffective tumor inducing agents. Tinsley et al (12) and Harr et al (13) conducted an extensive study on the chronic toxicity of selenium in rats. They reported no excess of neoplasms in rats fed selenite and selenate up to 16 ppm, even though hepatic toxicity was observed.

880

More recently, cytogenetic effects induced by i norgani c selenium have been reported. Nakamuro et al (14) noted that five selenium compounds induced various degrees of chromossmal aberrations in cultured human leukocytes as well as reactivity with DNA in Bacillus subtillis. Likewise, Lo et al (15) demonstrated the cytotoxicity of selenate and selenite to cultured human fibroblasts. Both groups of workers state that their results indicate a possible genetic hazard to humans from exposure to selenium compounds. Contrary to these results, Shamberger et al (16) noted incubated with sodium selenite human blood leukocyte cultures, and the carcinogen 7,12_dimethylbenz (a) anthracene (DMuH), had 42.0% fewer chromosomal breaks than cultures incubated with this carcinogen only. Selenite was more effective than the other three antioxidants tested in reducing chromosomal McKeehan et al (17) noted selenium breaks induced by DMBA. essentiality in proliferating clonal growth of human fetal lung fibroblasts. Optimum growth of clones occurred at 30nM selenious acid, while much higher concentrations It is interesting (1OuM) were toxic and growth limiting. to note that upon the nutritive evaluation of,three types of tissue culture growth media, selenium was found to be an serum undoubtedly being the major integral component (17)) source of selenium in the culture media.

that

in the in vitro systems reported The contrary results above may be explained in the doseof selenium compound used by Lo et al used. For example, the lowest exposure Similarly, (15) was 8x10-5M selenite and selenate. used 1.5x10-4M of their respective Nakamuro et al (14) However, compounds as the lowest concentration in exposures. Shamberger (16) noted that only 2.0~10-7~ of selenite was sufficient to reduce the carcinogen induced chromosomal McKeehan et al (17) noted peak stimulation of breaks. The obvious question of selenious acid. growth at 3x10 -8M a realistic is which level of concentrations represent By converting these values to mg/L (to exposure leveI? provide a basis for comparison with the selenium drinking water standard) it can be seen that the lower range in the Lo et al study, in which no effect was seen without activation, is 15.2 mg/L for selenate and 13.8 mg/L for selenite. Likewise, with the Nakamuro et al study, the lower “no effects” range for these two compounds was 30.2 mg/L selenate It was noted by Diplock (18) that, in 27.7 mg/L selenite. clinical signs of selenium toxicosis occurred when humans, daily intake of the element reached 0.1 to 0.2 mg Se/kg the equivalent of 3.5 to 7.0 mg/L water intake, body weight, 70 kg and the average daily assuming the average man weighs It is evident that the “no water intake is 2 liters/day. effects” levels in the in vitro studies by Lo et al (15) and Nakamuro et al (14)yeGch higher than the selenium Sakurai and Tsuchiya (19) levels known to be toxic in humans.

881

and

noted

that the average dietary intake of selenium is 50 to 150 the equivalent of 25 to 75 ug/L. T e concentration of selenite used by Shamberger (16), 2.0 x lo- 9 M or the equivalent is clearly more in line with normal human selenium of 35 ug/L, exposures. made that selenium Consequently , the statements constitutes a possible genetic hazard to man, can not be -justified in light of the aforementioned information, as the quantity of selenium necessary to produce cytotoxic effects is extremely toxic, if not fatal, to man.

ug/day ,

In addition to the unrealistic concentrations used in the Lo et al (15) and Nakamura et al (14)studies, other factors can not lend support to their conclusions. Auerbach (20) and Sobels (21) have indicated that in vitro tests tend to be oversensitive. Also, the IARC (22) has izicated that administered selenium is rapidly excreted under physiological conditions, this being due primarily to the homeostasis of the body in regulating essential minerals. Even in the kidney and liver, two organs that accumulate the highest levels of selenium, concentrations probably could never reach levels comparable to those used by Lo et al and Nakamuro et al in their in vitro studies even in _F the most unusual situations. Lo et al (15) erroneously stated that the [ARC (22) classified selenium as a carcinogen. Upon reviewing the IARC documents referenced in the LO et al report, the following conclusions were found. “Selenium compounds were tested in mice and rats by the oral route. Although in one experiment in rats, selenium produced an increase in the incidence of liver tumours, the available data are insufficient to allow an evaluation of the carcinogenicity of selenium compounds. The available data provide no suggestion that selenium is carcinogen in man . . .‘I Although the evidence challenging the conclusion that selenium is a carcinogen needs to be replicated, it is concluded on the basis of the studies reviewed here, that selenium should not be classified as a carcinogen. Case

#2:

A

pessible

anticancer

effect

of

selenium

Shapiro (8) noted 60 years which support the earliest studies, were possible antitumor that inherent systemic would limit the1 r use.

several studies published over the past an anticancer effect of selenium. In the suggestion that selenium compounds agents was made, but it became apparent toxicity from the dose of the compound In the studies reviewed by Silapiro

all (8)) selenium

demonstrated antitumor

but one exhibited

(23) an

that effect.

inorganic

or

organic

Clayton and Baumann (24) made the serendipitous discovery that selenium reduced tumor incidence in rats fed the carcinogenic azo dye, ml -methyl p-dimethylaminoazo benzene. While testing for a synergistic effect between selenium and the azo

882

ic

dye,

the researchers noted a 50% decrease in the incidence of tumors in this treatment group, as compared with rats given the azo dye only. Selenium was administered as sodium selenite (5 ppm) for a four week period which interupted eight weeks of azo dye exposure at the end of the fourth week. More recent laboratory work examining the antitumor effects of selenium has been advanced primarily by Shamberger. In one of his earlier studies (25) it was noted that certain antioxidants afforded protection against 7, 12-dimethyl benz(a) antracene (DIYBA) . Swiss mice were initiated with the carcinogen. Subsequently, sodium selenite and other antioxidants, including vitamin E, were topically applied with the promoter croton oil. The results clearly indicated that sodium selenitk was an effective agent against tumor formation, 735 times more effective than vitamin E. The researchers attributed the reduction in tumorigenicity to the powerful antioxidant effect of the selenium compound and indicated that antioxidants may inhibit early critical reduction-oxidation reactions necessary for tumor formation. Riley (26) advanced the Shamberger and Rudolf study further when he successfully demonstrated that sodium selenite completely nullified the promoting effect of It was noted that mast Compound Al, a component of croton oil. cell reactions reflect changes that are occurring in the upper during the promotion phase of carcinogenidermis of mouse skin, city. initiation with hydrocarbons, followed by Normally, promotion with Compound Al, resulted in the accumulation of mast cells in the connective tissue core of the papillomas appearing at 12 weeks. However, when sodium selenite was applied, no mast cell reactions occurred in either initiated nor noninitiated skin, and no tumors developed in these groups. Shamberger (27) repeated his earlier In another report, work and also tested the complete carcinogen 3-methylcholanthrene (MCA). In the selenium treated groups, there was a noticeable decrease in both per cent of mice with tumors Unfortunate1 y, and in the number of papillomas per mouse. the brief report failed to indicate which groups showed statisShamberger (28) used the carcinogens DMBA, tical significance. and benzo(a)pyrene (BAP) to test the effects of antioxidants MCA, Nondietary sodium selenite on skin papilloma formation in mice. significantly decreased applications, in concert with a promoter, tumor incidence. It was noted that even when the promoter was applied for 16 to 18 weeks following the cessation of the 2 out of 3 experimental groups had sodium selenite treatment, incidence. In the group that significant decreases in tumor failed to show statistical significance, there were still in the control group than twice as many papillomas per mouse Two other antioxidants, in the sodium selenite treated group. ascorbic acid and vitamin E, along with two lysosomal stabilizers, were also tested for inhibitory hydrocortisone and chloroquine, Shamberger noted that while effects against MCA induced tumors.

883

selenium was very effective in reducing the incidence of vitamin E was less effective, though it did produce tumors, The failure of statistical differences in some experiments. stabi 1 izers to reduce tumors, vitamin C and lysosomal suggested to the investigator that the protective action, of selenium and vitamin E is highly specific and probably not related to a general antioxidation mechanism. In the second Shamberger (28) examined the dietary part of the study, action of selenium in inhibiting tumor formation. Mice were fed torula yeast diets supplemented with 0, .l, and 1.0 Only those mice receiving the highest ration ppm selenite. of selenite showed statistically significant decreases in indicate that selenium exhibits These experiments tumors. an inhibitory effect on tumor promotion. The mechanism of this preventive action is still unclear. Some epidemiological evidence has suggested a negative correlation between selenium intake and the incidence of A study of 210 blood samples from 19 cities has cancer. demonstrated that human selenium blood levels varied in direct agreement with ambient forage and soil levels of this element (29). the range of blood levels was However, much narrower than the range of selenium found in forage. The reporters suggested that such tendencies towards uniformity in selenium blood levels may be due to a homeostatic mechanism regulating selenium content in blood or possibly it may be due to interregional movement of human food within the U.S. None the less, the conclusion that forage and soil levels of selenium are an indication of human blood levels in a particular area, serves to validate comparisons made between cancer rates and regional selenium levels. Shamberger has also done extensive work in relating incidence of cancer and death rates to geographic regions with high selenium in forage and soil. In a report by it was hypothesized that areas Shamberger and Frost (30) adequate or deficient in selenium should be expected to show different disease incidences or death rates. The researchers obtained maps showing the distribution of selenium in the as determined by forage crops. U.S. Death rates for several states were also obtained. The researchers noted that 31 states with an average forage crop concentration of .O6 ppm or more had significantly lower death rates for 1965 than 17 states where forage crop concentrations were .05 5 After sex and age adjustment, death rates Ps:r ppm or less. 10 156.5 (171.5 males and 142.0 females) for the high selenium states and 179.0 (191.0 males and 165.5 females) for the low selenium states. These rates are for all causes and not In a similar study in Canada, data just cancer death rates. indicated that the death rates in high selenium areas was while the death rate in low selenium regions was 122,2+7.8, It was not reported if these results were 139.9t4.9 (p indicated that “sudden death syndrome” in lambs and pigs is He noted that active associated with selenium deficiency. rapidly in selenium deficiency than muscle degenerates more does inactive muscle. Selenium has been shown to be an integral part of several For isolaced from animals and bacteria. proteins and enzymes isolated a protein from the muscle Whanger et al (51) example, Stadtman (52) noted that of selenium supplemented lambs. spectral analysis of a selenoprotein isolated from lamb muscle similar to chromophere indicated the presence of a heme group This suggested that the selenoprotein was of cytochrome c. Burke and involved in electron transfer in redox reactions. Consolazio (53) noted that a selenium binding protein was in the plasma of rats receiving .5 ppm much more prominent than in rats receiving no supplemental selenium. of the element, Rotruck glutathione Ultimately, and extracted an integral peroxidase

observed a reduction et al (54) peroxidase in selenium deficient when the researchers injected this enzyme, they discovered component of this enzyme (55). maintains reduced glutathione,

889

of rat

the enzyme erythrocytes. into the rats i’5,, that selenium was Glutathione which in turn,

prevents of many glutathione selenium.

chemically induced including species, peroxidase and

oxidative damage to membranes Oh et al (56) purified man. noted that it contained .34%

Shrift (57) listed several selenocompounds that have The significance been reported to occur in microorganisms. discussed and it was suggested of some of these compounds was is forthcoming and should that testing with microorganisms help provide answers to questions on selenium biochemistry. Stadtman (52) reviewed studies where functional selenoproteins The activity of the enzyme were identified in bacteria. in the oxidation of formate to carbon formate dehydroqenase dioxide in Clos;ridium thermoaceticum was shown to be selenium have identified selenium as an Studies with 75Se dependent. Iron and molybdenum were also integral part of this enzyme. All three of these identified as components of this enzyme. in the electron transfer elements were thought to participate precess of the formate dehydrogenase mediated oxidation Another low weight selenoprotein was identified reaction. Selenium part of the clostridial glycine reductase system. in the electron transfer was demonstrated to participate that leads to the synthesis of ATP in the bacteria. process

as

The potential of selenium to reduce the toxicity of some Mason and Young (58) examined the metals has been studied. effectiveness of zinc and selenium in protecting against Selenium reduced the cadmium induced injury to rat testes. :njurious effects of cadmium when injected 2,6, and 12 hours the rapid rate of absorption and before cadmium. Apparently, Ganther excretion of selenium account for these observations. and Sunde (59) reported that selenium reduces mercury toxicity in quail, substantiating an earlier claim by Parizek and Ostadalova (60) that selenite reduced the acute toxic effects of mercuric chloride in rats. There is evidence that selenium and vitamin E have an interactive effect in protecting biological membranes. Nelson et al (61) noted in their experiments with beef calves that only the combination of vitamin E and selenium would reduce the incidence of nutritional muscular dystrophy. Either nutrient alone would not alleviate the symptoms. Thompson and Scott (62) demonstrated that selenium protected against exudative diatheses in the chick. However, the level of selenium required for protection was inversely related to the level of vitamin E in the diet. For example, when 100 ppm vitamin E was added to the diet, less than . 01 ppm selenium was sufficient to prevent the disease. However, when only 10 ppm vitamin E was present in the feed, over .02 ppm seleniun was required to afford protection against the disease. Combs et al (63) reviewed the protective effects of selenium and vitamin E. The concert function of these two nutrients was noted in preventing excessive lipid peroxidation in hepatic

890

microsomes of only if vitamin Either nutrient

newly hatched chicks. E and selenium were alone was ineffective

Peroxidation was prevented present in the feed. in preventing the effect.

Tappel and Caldwell (64) examined the reductionoxidation properties of selenium compounds in biochemical systems. They described five general redox reactions in which selenium involvement has been experimentally supported. 1) Selenium may act as a primary lipid antioxidant by rapidly removing the free radical intermediates in peroxidation reactions. Selenoproteins from kidney and liver tissue of chicks, rats, and sheep receiving supplemental selenium in their diets, have been shown to inhibit the oxidation of linoleic acid emulsions 20% to 500% more effectively than proteins from controls not given supplemental selenium. Furthermore, it was noted that selenoproteins seem to be 50 to 500 times more effective than vitamin E as peroxidative inhibitors (65). 2) Selenium may also act as a primary lipid antioxidant by decomposing lipid peroxides through non-radical mechanisms& Tests with methionine, cystine, and their selenium have indicated that selenocystine induced more analogs extensive decomposition of lipid peroxides than the other It was further mentioned that even though compounds tested. 85% of the selenocystine in the model system was transformed to other products within one minute after addition of peroxides decomposition of lipid peroxides continued for two hours, indicating an antioxidant effect of selenocystine metabolites. In addition, under certain conditions, selenocystine can be regenerated, indicating a catalytic reaction rather than a 3) Selenium compounds may stoichiometric mechanism (66). also act as aqueous free radical traps by scavenging free radicals and neutralizing them before damage is inflicted. 4) As compared with sulfer amino acids, the analogous selenium amino acids have been demonstrated to afforri better protection against radiation induced damage to proteins and amino acids (64). the protective effect of selenomethionine was Specifically, it was found that this compound is noted, and in addition, itself more stable and destroyed to a lesser extent than “the finding irradiation. 5) Finally, methionine, following that selenocystine stimulates oxidation of low molecular weight thiols while protecting sensitive sulfhydryl enzymes suggests that selenium compounds function in the maintenance Morris and Levander (67) of sensitive sulfhydryl. groups” (64). have provided evidence that selenium acts to protect -SH groups of mitochondrial membrane proteins. Oldfield et al (42) have reviewed some reports on in young children marked by slow growth kwashiorkor, a disease due to nutritional deficiencies, and to a certain extent, Selenium blood levels of infected children infectious agents. Selenium were found to be one half of the normal range. administered as sodium selenate was often effective in Hopkins and Majaj (68) stimulating growth in these children. in five children suffering reported reduced growth rates

891

from Kwashiorkor. recovered following also gave evidence response in anemia

All five of these undernutrition cases selenium treatment. The researchers that selenium can stimulate reticulocyte resulting from this svndrome.

There are no other known diseases in man related to selenium deficiency, oresumablv because the normal human diet contains sufficient selenium in eggs, milk. meats. and fish. Frost (50) sugaested a possible relationship between selenium and cardiovascular disease. It was noted that an inverse relationship existed between early heart mortality and selenium distribution in the U.S. However. no methodoloay was presented and the basis for this comparison is questioned. as no attempt at controlling for alternate factors was mentioned. -Summary

and

Conclusions

There is no evidence that selenium is carcinoaenic at nontoxic levels. Even evidence of selenium carcinogenicity at toxic doses experimental and is not convincing. In fact, indicate that dietary selenillm may epidemiological evidence provide enhanced protection against carcinogenesis. Epidemiological evidence that hiah selenium levels increase the rates of dental caries is not consistant with experimental data in laboratory animals. Further examination of these epidemiological studies has shown that workers failed to control for the factors that prominently effect caries formation such as dietary habits, personal hyqiene practices, and socioeconomic status. Due to this lack of proper-Iv matched comparison qroups in these studies, it is not possible to establish a causal link between selenium intake and dental caries formation. Presently there is amole evidence clearly demonstratina the essentiality of selenium. N0 n e 0 f this evidence was taken into consideration in promulgating the current national drinking water standard for selenium (10 ug/L). Clearlv, the criteria used bv the USPHS in 1962 and then again by the EPA in 1977 to set the drinking water standard for selenium at IO ug/L can not be justified with current biomedical and epidemiological findings. Utilizinq both animal and human data and incorporating a safetv factor of 10, Sakurai and Tsuchiya (19) proposed a value of 500 us/day as the acceptable dai Iv human intake limit for selenium from all sources. I il supoort of this proposal. these researchers noted that a Japanese diet of fish and shellfish contains as much as 225 ug/dav of selenium and possibly as much as 500 ug/day in extreme cases, there have been no reported cases of seleni urn toxi ci tv from vet such diets. The National Research Council (69) seemed to be i nd i ca ted somewhat They in aareement with this 500 ug/dav limit. that the maximum no observed health effects level for sele!iium

8%

is not in water less than 100 ug/l~ and probably as great 500 ug/L (assuminq normal human consumption is 2 liters/day, this estimate is approximately equivalent to 1000 uo/day).

as

With the present 10 us/L drinking water standard, selenium intake via water can not exceed 20 uq/day, assuming the average water intake is 2 liters/day. The NRC (69) estimated that 20 uq/L of selenium or the equivalent of 40 uq/day (assuming 2 liters/day intake) is the minimum amount of this element required bv the body to sustain normal health. It is evident that the current standard of 10 ug/L prevents the use of potable water supplies that contain less that this minimum required amount of selenium, clearly an untenable position. It

understood that the purpose of a drinkina water maximum limit concentration) is to protect the as well as those at increased risk, from developing any adverse health effects (e.g. toxicity, carcinogenicity, teratogenicitv, etc.) from the substance in An acceptable total intake question to the extent feasible. level of 500 ug/dav has been established by one aroup of rethis level should be considered searchers (19). In addition, as there are no known sensitive acceotable to all grouos of people, seqments of the population who are at high risk to selenium A maximum limit at normally encountered levels of exposure. to no areater than 20 percent concentration which permi ts exposures limit from al 1 sources (500 ug/ (100 ug/day) of the acceptable day) is sufficient to protect the public from excessive exposure In terms of a drinking water standard, this limit to selenium. would be equivalent to 50 uq/L or .05 ppm (assuming the average In support of this daily consumption of water is 2 L/dav). standard general

must (i.e. oublic.

be

a recent report (70) noted that there were no proposa 1, in as measured bv 85 health parameters, health effects. Colorado community whose drinking water supply contained in the ranqe of 50 to 125 us/L as compared to a similarly that 50 we propsoe Therefore, group with ( 16 ug Se/L. should be tFe standard promulgated bv the EPA.

893

adverse a selenium matched ug/L

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I .

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Shamberger RJ, Baughman FF, Kalchert SL, Willis CE, Carcinogen-induced chromosomal breakage Hoffman GC. decreased by Antioxidants Proceedings: National Academy Science 70:1461-1463, 1973.

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