A.L. Moxon Honorary Lectures

Special Circular 167-99

Toxicity Studies in South Dakota

Ivan S. Palmer
South Dakota State University
Brookings, SD 57006.

Introduction

The Chemistry Department at South Dakota State College (now University) was separated from the Experiment Station Chemistry group in 1926, and Dr. K.W. Franke was named Director of the Experiment Station Biochemistry Department. In 1929, Dr. Franke began work on the "Alkali Disease" problem which occurred in farm animals in certain parts of the state. Although previous work had been done on this malady, the cause was unknown. During the next four years, cooperative research with the USDA led to selenium being designated as the component in natural toxic grains, which produced the signs of alkali disease in animals. A.L. Moxon began working on the selenium project in January, 1930 (Moxon, 1937a). Dr. Franke died September 15, 1936, and Dr. Moxon succeeded him as Head of the Experiment Station Biochemistry Department. Dr. Moxon's work on the South Dakota selenium project from 1930 to 1950 has been published in numerous national journals, in Experiment Station Bulletins, in the South Dakota Academy of Science and in other local publications. The volume and importance of his contributions are truly outstanding, especially in the light of the cumbersome methods of analysis and limited funding.

Prior to reviewing Dr. Moxon's contributions to the understanding of selenium toxicity, it is important to draw attention to another impact that is seldom noted. Dr. Moxon and his colleagues were very successful in attracting and employing a number of young people who later went on to establish distinguished careers in science. This is well illustrated by quoting from the Foreword in one of his early publications (Moxon, 1937a).

"......The project was started in 1929 and several people have added to the mass of information during the time that they were employed in this department. The following should be mentioned for their contributions: Mrs. John Liska (Miss Florence Marx), Mr. Van R. Potter, Mr. E. Page Painter, Mr. Robert Burris, Mr. Robert Hutton, Mr. Morris Rhian, Mr. Harlan Anderson and Mr. Wesley Ruth......"

In addition to the names listed in the above quotation, several other student names appear on early publications: K.P. DuBois, D.F. Peterson, H.A. Lardy, O.E. Olson, A.E. Schaefer, A.W. Halverson, E.I. Whitehead, Orville Bentley and many others. Perhaps one of Dr. Moxon's greatest contributions has been his ability to enlist and excite these students who have gone on to make significant contributions in a variety of fields.

Soon after the discovery by Franke (1934) that the toxic principle in South Dakota grains was associated with the protein fraction, Franke and Moxon (1934) began to look for a more rapid system to assay for the toxic protein. Feeding studies using growth as the indicator of toxicity were effective but slow. Franke and Moxon followed the lead of others in using the effect on yeast fermentation/CO₂ production as their assay system. They were able to show that isolated protein from normal corn or wheat would stimulate CO₂ production, whereas toxic proteins (corn 523, wheat 582) would give no stimulation of fermentation. They later devised a system that made the measurement of CO₂ production more convenient (Franke and Moxon, 1934a).

The elemental content of the toxic proteins used in the South Dakota studies was studied by other workers. In 1933, Robinson found that a sample of toxic wheat protein contained selenium, and in 1934, Byers showed that another toxic wheat protein (wheat 582) contained high levels of selenium and vanadium. These findings implicated Se as the toxic principle and led Moxon and Franke (1935) to study the effect of some inorganic salts of these elements on enzyme activity as measured by CO₂ production in yeast. They found that the selenium salts did indeed inhibit fermentation. The order of toxicity of the different salts was sodium selenite > sodium selenide > sodium selenate. The yeast fermentation assay system was not often used in subsequent studies.

Characterization of Selenium Toxicity

Once Se was implicated as the toxic component in feeds which caused alkali disease, studies delineating the magnitude and nature of the toxicity were rapidly designed and executed. Franke and Moxon (1936) determined the minimum fatal dose (MFD) of selenium and several other elements by intraperitoneal injection into rats. The data in Table 1 have been quoted extensively, and although many subsequent studies have been conducted, the accepted toxicity values for sodium selenite and sodium selenate have not been changed much from those in Table 1. In the same time period, various levels of selenium salts were injected into the air cells of fertile hen's eggs and heavy mortality resulted (Franke et al., 1936). In those instances where embryos developed, monstrosities were produced similar to those obtained from hatching eggs produced by hens fed toxic grain.

In 1936, Dr. Moxon was named Head of the Department of Experiment Station Biochemistry following the death of K.W. Franke. He was author of an Experiment Station Bulletin in 1937 (Moxon, 1937a) that summarized most of the work done on selenium up to that time. The summary included some of the work reported in other journals, but it also included several pictures of selenized animals and some data that were not reported elsewhere. The Summary and Conclusions section of the Bulletin stated that selenium poisoning in South Dakota was primarily the chronic type referred to as "alkali disease". The general symptoms were listed as:

1. Dullness and lack of vitality
2. Emaciation and rough coat
3. Atrophy of the heart (dish-rag heart)
4. Atrophy and cirrhosis of the liver
5. Anemia
6. Erosion of the long bones, especially the joints, which causes stiffness
7. Loss of the long hair from the mane and tail of horses and from the switch of cattle. Loss of hair from the body of hogs
8. Soreness and sloughing of the hoofs

In 1938, Dr. Moxon published a short note in Science that described an antagonistic effect of arsenic on selenium toxicity. No tabular data were given, but the article stated that 5.0 ppm As as sodium arsenite in the drinking water of rats fed 15.0 ppm Se in the form of Se-wheat gave complete protection against liver damage. Arsenic at 2.5 ppm gave only partial protection. The authors stated that feeding arsenic to livestock was not recommended, but it was hoped that other less toxic elements would prove to be effective. The publication of this article started a series of studies over several decades that attempted to elucidate the mechanism of the Se-As antagonism. This review of Dr. Moxon's work has been essentially chronological up to this point. His other contributions will be organized and reviewed by subject matter.

A series of articles by Franke and coworkers on the effects of the new toxicant in grains fed to poultry was published in 1935-36 (Franke and Tully, 1935; Tully and Franke, 1935; Franke and Tully, 1936). These studies demonstrated the reduced growth of chicks caused by toxic grains, and also showed that hens fed the toxic grains produced eggs with poor hatchability due to deformation of the chicks. Moxon began working with the group, and they injected selenium salts into the air cells of fertile eggs. They found that selenium salts reduced hatchability and produced the same monstrosities that were obtained from eggs produced by hens receiving toxic grains (Franke et al., 1936). Continuing the work with poultry, Poley et al. (1937) showed that feeding selenium grains (15 ppm Se) would cause weight loss in laying hens, although egg production and fertility were not affected. Feed consumption was appreciably lowered. Hatchability decreased to zero when toxic grains were fed. No normal chicks were hatched after the 7^th day of feeding the selenium-containing grain. After restoring normal grain to the diet for 6 days, normal embryo development and hatchability returned. Elemental sulfur at 1% of the diet did not affect the action of selenium.

Moxon and Poley (1938) established levels of selenium that could be tolerated by poultry fed selenium grains. They showed that chickens fed diets containing <2.5 ppm Se produced eggs and meat below 4.0 ppm (tolerance limit as proposed by Byers, 1936). Poley and Moxon (1938) also found that hatchability and fertility were normal at 2.5 ppm. At 5.0 ppm Se in the diet, there was a slight effect on hatchability, and at 10.0 ppm Se, hatchability was reduced to zero. Growth and mortality were not affected at 5.0 ppm but there were serious effects at 10.0 ppm. Further studies with poultry (Poley et al., 1941) led to the recommendation that diets should not include more than 5.0 ppm Se.

In an attempt to find a means of controlling the toxic effects of selenium, Moxon et al. (1940) administered bromobenzene to dogs fed diets made from seleniferous grains and to alkalied steers, which had been grazing on seleniferous range. The bromobenzene greatly increased the urinary excretion of selenium and the toxic signs seemed to be reduced. Further work was done with dogs (Moxon, 1941), and Moxon and Olson (1940) reported that rats also responded to bromobenzene administration. Bromobenzene has not been used in the practical treatment of alkali disease.

Early studies on the effect of protein on selenium toxicity in rats showed that high protein diets tended to give more protection against the toxic effects of selenium than low protein diets (Moxon, 1937). In an attempt to determine whether or not protein from different sources might have differing responses, Moxon (1941) partially substituted various proteins in toxic diets as part of the work for his Ph.D. dissertation. Both rats and dogs were fed rations containing 10.0 ppm Se and various proteins were substituted. The proteins used were as follows: crude casein, linseed meal, tankage, corn gluten meal, meat scraps, soybean meal, cottonseed meal, purified casein, whole milk powder, and dried whole beef liver. Only linseed meal gave protection to both rats and dogs. The protective effect of linseed meal against selenium toxicity also was demonstrated in poultry (Anderson et al., 1941). Linseed meal was used to minimize selenium toxicity in cattle on seleniferous range, and it was generally assumed that the protection was a function of the protein. The mechanism of protection was finally resolved in 1979 to 1980 by other workers at the South Dakota Experiment Station. The protective factors were isolated and purified (Palmer et al., 1980) and identified as the cyanogenic glycosides, linustatin and neolinustatin (Smith et al., 1980).

Moxon also provided some of the first data on excretion of selenium by animals (Anderson and Moxon, 1941) and the distribution of selenium in animal tissues (Anderson and Moxon, 1942; Moxon and Rhian, 1943; Moxon et al., 1947). Dogs were used as the experimental animal so that adequate tissue could be obtained for analysis, because analytical methodology lacked sensitivity. The work was impressive because of the cumbersome analytical methods available at that time.

Toxicity of Organic Selenium Compounds

Painter and Franke (1935) demonstrated that the selenium in toxic cereal grains was in an organic form and appeared to be located in the protein. It appeared advisable to study the toxicity of various organic compounds, but few were available at that time. Several compounds were prepared by E.P. Painter (Moxon et al., 1938) and fed to rats. All compounds showed some toxicity based on growth reduction. However, they were much less toxic than selenium in cereal grains or inorganic selenium. The organic compounds also were used to determine the minimum fatal dose (MFD) when injected i.p. into rats. The MFD was defined as the dose required to kill 75% of the animals in 48 hours. Data for four compounds are shown in Table 2. As with the feeding experiments, the compounds in Table 2 were much less toxic than inorganic selenium (Franke and Moxon, 1936).

As part of the work for his Ph.D. dissertation, Moxon (1941) obtained several organic selenium compounds, including selenocystine, from Dr. Arne Fredga of Uppsala University, Uppsala, Sweden. Moxon and Schaefer (1940) studied the chemical stability of selenocystine during electrodialysis and acid hydrolysis and demonstrated the compound was unstable under certain conditions. Moxon (1940) then determined the MFD of all the compounds which were administered i.p. to rats. The data are shown in Table 3. Obviously, selenocystine was one of the most toxic organic compounds that had been observed up to this time. In later studies, Dr. Moxon was able to obtain optically active enantiomorphs from Dr. Fredga (Moxon, 1941). These compounds were fed to rats at the level of 18.0 ppm Se (Moxon et al., 1941). Optically inactive cystine was similar in toxicity to Se-wheat, and selenite was slightly more toxic. The d-form of selenocystine was about one-third as toxic as the l-form. The l-selenocystine was the most toxic Se compound observed up to this point. In 1949, Klug et al. confirmed that the toxicity of Se-cystine, administered by i.p. injection to rats, was 4.0 mg Se/kg. In addition, they showed the toxicity of selenomethionine was 4.25 mg Se/kg. In the same study, the authors demonstrated that Se-cystine was very toxic to the liver succinoxidase system but that Se-methionine was not. A few other studies on the toxicity of Se-cystine were conducted by Moxon's group (Klug et al., 1950c; Klug et al., 1952).

Selenium-Arsenic Antagonism

Immediately following the publication of the short note in Science, which reported the protective effect of arsenic against selenium toxicity (Moxon, 1938), a large number of studies were initiated to elucidate the mechanisms of this antagonism. Lardy and Moxon (1939) showed that arsenite prevented inhibition of yeast fermentation caused by selenite. Arsenate and arsenite tended to increase the toxicity of selenate in this system. Moxon and DuBois (1939) administered 5 ppm arsenic and several other elements in the drinking water of rats to study their effect on 11 ppm selenium as Se-wheat. Fluorine, molybdenum, chromium, vanadium cadmium, zinc, cobalt, nickel and uranium all increased the observed toxicity in the selenium-treated groups. Tungsten gave some protection against liver damage and mortality, but complete prevention of selenium toxicity was only obtained with 5.0 ppm As as sodium arsenite. Other studies (Potter et al., 1939) demonstrated that arsenic in the diet would maintain liver glycogen stores in selenized rats at levels similar to the controls and much higher than in animals receiving just selenium. DuBois et al. (1940) showed that administering 5.0 ppm As to rats, from either arsenite or arsenate, was effective in overcoming the effects of 11.0 ppm Se from Se-wheat, but arsenic sulfide was not effective. The authors stated (unpublished data) that arsenite was protective against Se from Se-wheat, selenite and selenocystine. This study also showed that arsenic would protect rats that had previously been fed selenium diets for 20 days, but it was ineffective if the selenium had been fed 30 days prior to the arsenic administration. Moxon and coworkers also demonstrated that arsenic would overcome the toxicity of selenium in hogs (Moxon, 1941a), dogs (Moxon, 1941; Rhian and Moxon, 1943) and poultry (Moxon and Wilson, 1944; Carlson et al., 1951). In order to find less toxic forms of arsenic, the group started studies on the effectiveness of organic arsenicals against selenium toxicity (Moxon et al., 1947).

Moxon and coworkers began studying the effect of arsenic on selenium distribution in rats (Moxon et al., 1945; Klug et al., 1950; Petersen et al., 1950) even before the use of radioisotopes became popular for such studies. Moxon and his group never determined the mechanism of the Se-As antagonism, but they did suggest that it was not due to an interference with absorption. Many years later, Carl Baumann's group at the University of Wisconsin demonstrated that arsenic greatly increased the biliary excretion of selenium in selenized animals (Ganther and Baumann, 1964; Levander and Baumann, 1969; Levander, 1972).

Mapping Seleniferous Areas and Availability of Selenium to Plants

After the identification of selenium as the toxic principle in certain poisonous grains, the South Dakota Experiment Station began extensive sampling of the geological formations in South Dakota. Some of the first results were given in the early Experiment Station Bulletin 311 (Moxon, 1937). The amount of field work and the number of samples analyzed during this time are truly remarkable. An annual Experiment Station report for the period of July 1, 1939 to June 30, 1940 states that a total of 2688 selenium analyses were performed (Moxon and Olson, 1940). This is a phenomenal number considering the cumbersome methods of analysis available at that time. To give some perspective to the magnitude of output of these early workers, the current annual sample output, with a semi-automated method, is 4,500 to 6,000 samples. The dedication of Dr. Moxon is well illustrated in local folklore. Apparently, when Dr. Moxon was married, he and his bride planned to make a honeymoon trip to the western part of the state. Not wanting to miss an opportunity to sample the high selenium areas, he took a young man along on the honeymoon to assist in the sampling. The young man was Oscar E. Olson (Personal communication, Elaine Olson, Brookings, South Dakota.) Now that is dedication!

Much of the early work was described as being of a "reconnaissance nature" (Moxon and Rhian, 1943). Geological formations known to be seleniferous and "indicator" plants were used to guide sampling in these surveys. Moxon and coworkers, in cooperation with the South Dakota Geological Survey and other agencies, analyzed well cores and samples of other known origin (Moxon, 1937; Moxon et al., 1938; Searight et al., 1947; Moxon et al., 1950) and established that the Pierre and Niobrara formations were the main sources of highly seleniferous material. In fact, the toxic grains studied by Franke were obtained from the Pierre Shale areas (Moxon, 1937). Most of the outcroppings of these formations occurred in areas of South Dakota west of the Missouri River, and much of the mapping of high selenium areas has been done in that area. However, the Experiment Station group did survey the glacial deposits in the eastern part of the state (Searight and Moxon, 1945; Searight et al., 1946). Relatively few areas were found that would cause selenium toxicity problems.

Olson and Moxon (1939) studied the availability of selenium in the soil from six different seleniferous areas. Regardless of the soil types, the uptake of selenium by corn, wheat or oats was dependent on the amount of water-soluble selenium. There also seemed to be a correlation with the amount of organic matter in the soil. Little correlation was found between the amount of selenium in the crops and the total selenium or acid-soluble selenium in the soil.

The Resettlement Administration, Land Utilization Division, made available a three-section ranch in Lyman County (South Dakota) to be used for selenium research. The site was called the Reed Ranch and was located in one of the most seleniferous areas of the state. Moxon and coworkers used the ranch to do some very detailed mapping of the selenium in soils and then attempted correlation of soil selenium with plant selenium content. Olson et al. (1942), using the detailed maps of the soil selenium content on the experimental ranch, studied the effect of stage of growth on the selenium content of various species of plants. The selenium content of plants remained quite constant through various stages of growth, but after maturity, it decreased rapidly. The workers found that it was difficult to find consistent differences in selenium content of plants between different growing seasons. This study also provided evidence that western wheat grass (Agropyron smithii) appeared to be a relative index to the amount of available selenium in the soil. Olson et al. (1940; 1942) also studied the availability of soil selenium to plants at the same ranch. They found again that soluble selenium was important in determining the amount of selenium uptake by plants, and that the second and third foot of soil might be the most important source of selenium for plants. They also pointed out that large variations in plant content may occur over short distances on soils apparently derived from the same parent material. Searight et al. (1947) used the same techniques to perform detailed studies relating selenium content of wheatgrass to soil profile. Generalizations from the above studies are still used today to help ranchers manage seleniferous ranges.

The unique Reed Ranch provided several opportunities to study livestock growth and reproduction on a natural selenium range that could be closely managed. Several studies were conducted while Dr. Moxon was at the Experiment Station (Moxon, 1937; Moxon and Olson, 1940; Moxon et al., 1944) and others continued the work for many years. The ranch is no longer a part of the Experiment Station.

Miscellaneous Studies

Several other studies were conducted during Dr. Moxon's service to South Dakota that do not fit the categories mentioned above. They include: the effect of selenium toxicity on glutathione levels (DuBois et al., 1939); the absorption of arsenic by plants (Olson et al., 1940); the arsenic content of cretaceous formations (Moxon et al., 1944); the distribution of selenium in milled wheat (Moxon et al., 1943); the ascorbic acid content of livers of selenized rats and chicks (Lardy and Moxon, 1942); the glutathione and ascorbic acid values in selenium poisoning (Klug et al., 1950a); the inhibition of succinic dehydrogenase (Klug et al., 1950b; 1953); and the studies on the effect of ACTH in selenium intoxication (Petersen and Moxon, 1951).

Summary

References

Anderson, H.D. and A.L. Moxon. 1941. The excretion of selenium by rats on a seleniferous wheat ration. J. Nutr. 22:103.

Anderson, H.D. and A.L. Moxon. 1942. Changes in the blood picture of the dog following subcutaneous injections of sodium selenite. J. Pharmacol. Exp. Therap. 76:343.

Anderson, H.D., W.E. Poley and A.L. Moxon. 1941. The effect of dietary protein supplements on the toxicity of seleniferous grains for the chick. Poultry Sci. 20:454.

Byers, H.G. 1934. Ind. Eng. Chem., News Ed. 12:22. Taken from Moxon and Franke (1935).

Byers, H.G. 1936. Selenium occurrence in certain soils in the United States with a discussion of related topics. Second Report, USDA Tech. Bull. 530.

Carlson, C.W., W. Kohlmeyer and A.L. Moxon. 1951. Arsenic fails to control selenium poisoning in turkeys. South Dakota Farm and Home Res. 3:20.

DuBois, K.P., A.L. Moxon and O.E. Olson. 1940. Further studies on the effectiveness of arsenic in preventing selenium poisoning. J. Nutr. 19:477.

DuBois, K.P., M. Rhian and A.L. Moxon. 1939. The effect of glutathione on selenium toxicity. So. Dak. Acad. Sci. 19:71.

Franke, K.W. 1934. A new toxicant occurring naturally in certain samples of foodstuffs. J. Nutr. 8:597.

Franke, K.W. and A.L. Moxon. 1934. A new toxicant occurring naturally in certain samples of plant foodstuffs. IV. Effect of proteins on yeast fermentation. J. Nutr. 8:625.

Franke, K.W. and A.L. Moxon. 1934a. An apparatus for determining the rate of carbon dioxide production during yeast fermentation. J. Biol. Chem. 105:415.

Franke, K.W. and A.L. Moxon. 1936. A comparison of the minimum fatal doses of selenium, tellurium, arsenic and vanadium. J. Pharmacol. Exp. Therap. 58:454.

Franke, K.W. and A.L. Moxon. 1937. The toxicity of orally ingested arsenic, selenium, tellurium, vanadium and molybdenum. J. Pharmacol. Exp. Therap. 61:89.

Franke, K.W., A.L. Moxon, W.E. Poley and W.C. Tully. 1936. Monstrosities produced by the injection of selenium salts into hens' eggs. Anat. Rec. 65:15.

Franke, K.W. and W.C. Tully. 1935. A new toxicant occurring naturally in certain samples of plant foodstuffs. V. Low hatchability due to deformities in chicks. Poultry Sci. 14:273.

Franke, K.W. and W.C. Tully. 1936. A new toxicant occurring naturally in certain samples of plant foodstuffs. VII. Low hatchability due to deformities in chicks produced from eggs obtained from chickens of known history. Poultry Sci. 15:316.

Ganther, H.E. and C.A. Baumann. 1964. Selenium metabolism. I. Effects of diet, arsenic and cadmium. J. Nutr. 77:210.

Klug, H.L., R.D. Harshfield, R.M. Pengra and A.L. Moxon. 1952. Methionine and selenium toxicity. J. Nutr. 48:409.

Klug, H.L., G.P. Lampson and A.L. Moxon. 1950. The distribution of selenium and arsenic in the body tissues of rats fed selenium, arsenic, and selenium plus arsenic. So. Dak. Acad. Sci. 29:57.

Klug, H.L., A.L. Moxon and G.P. Lampson.1950a. Glutathione and ascorbic acid values in selenium poisoning. So. Dak. Acad. Sci. 29:16.

Klug, H.L., A.L. Moxon and D.F. Petersen. 1950b. The in vivo inhibition of succinic dehydrogenase by selenium and its release by arsenic. Arch. Biochem. 28:253.

Klug, H.L., A.L. Moxon and D.F. Petersen. 1950c. The effect of selenium, cystine and low protein diets on rat tissue glutathione and ascorbic acid levels. So. Dak. Acad. Sci. 29:38.

Klug, H.L., A.L. Moxon, D.F. Petersen and E.P. Painter. 1953. Inhibition of rat liver succinic dehydrogenase by selenium compounds. J. Pharmacol. Exp. Therap. 108:437.

Klug, H.L., D.F. Petersen and A.L. Moxon. 1949. The toxicity of selenium analogues of cystine and methionine. So. Dak. Acad. Sci. 28:117.

Lardy, H.A. and A.L. Moxon. 1939. The effect of selenium and arsenic at various ratios on the fermentation of glucose by baker's yeast. So. Dak. Acad. Sci. 19:109.

Lardy, H.A. and A.L. Moxon. 1942. The ascorbic acid content of the livers of selenized rats and chicks. So. Dak. Acad. Sci. 22:39.

Levander, O.A. 1972. Metabolic interrelationships and adaptations in selenium toxicity. Ann. N.Y. Acad. Sci. 192:181.

Levander, O.A. and C.A. Baumann. 1969. Selenium metabolism. V. Studies on the distribution of selenium in rats given arsenic. Toxicol. Appl. Pharmacol. 9:98.

Moxon. A.L. 1937. The effects of diets containing selenium in the form of seleniferous grains and inorganic salts on the blood picture of the dog and the selenium content of the tissues and organs of these animals. M.S. Thesis, South Dakota State College, Brookings, 61p.

Moxon, A.L. 1937a. Alkali disease or selenium poisoning. So. Dak. Agric. Exp. Sta. Tech. Bull. No. 311, 91 p.

Moxon, A.L. 1938. The effect of arsenic on the toxicity of seleniferous grains. Science 88:81.

Moxon, A.L. 1940. Toxicity of selenium-cystine and some other organic selenium compounds. J. Amer. Pharm. Assoc. 29:249.

Moxon, A.L. 1941. Some factors influencing the toxicity of selenium. Ph.D. Dissertation, University of Wisconsin, Madison.

Moxon, A.L. 1941a. The influence of arsenic on selenium poisoning in hogs. So. Dak. Acad. Sci. 21:34.

Moxon, A.L., H.D. Anderson and E.P. Painter. 1938. The toxicity of some organic selenium compounds. J. Pharmacol. Exp. Therap. 63:357.

Moxon, A.L. and K.P. DuBois. 1939. The influence of arsenic and certain other elements on the toxicity of seleniferous grains. J. Nutr. 18:447.

Moxon, A.L., K.P. DuBois and R.L. Potter. 1941. The toxicity of optically inactive d- and l-selenium cystine. J. Pharmacol. Exp. Therap. 72:184.

Moxon, A.L. and K.W. Franke. 1935. Effect of certain salts on enzyme activity. Effect of sodium selenate, selenite, selenide, tellurite, sulfate, sulfite, sulfide, arsenite and vanadate on rate of carbon dioxide production during yeast fermentation. Ind. Eng. Chem. 27:77.

Moxon, A.L., C.W. Jensen and C.R. Paynter. 1947. The influence of germanium, gallium, antimony and some organic arsenicals on the toxicity of selenium. So. Dak. Acad. Sci. 26:21.

Moxon, A.L. and O.E. Olson. 1940. Livestock diseases, parasites and poisoning: Can selenium poisoning of livestock be checked? Farm Home Res. So. Dak. 53:42.

Moxon, A.L., O.E. Olson and W.V. Searight. 1950. Selenium in rocks, soils and plants. So. Dak. Agric. Exp. Sta. Tech. Bull. 2:5.

Moxon, A.L., O.E. Olson, W.V. Searight and K.M. Sandals. 1938. The stratigraphic distribution of selenium in the cretaceous formations of South Dakota and the selenium content of some associated vegetation. Am. J. Bot. 25:794.

Moxon, A.L., O.E. Olson, E.I. Whitehead, R.J. Hilmoe and S.N. White. 1943. Selenium distribution in milled seleniferous wheats. Cereal Chem. 20:376.

Moxon, A.L., C.R. Paynter and A.W. Halverson. 1945. Effect of route of administration on detoxification of selenium by arsenic. J. Pharmacol. Exp. Therap. 84:115.

Moxon, A.L. and W.E. Poley. 1938. The relation of selenium content of grains in the ration to the selenium content of poultry carcass and eggs. Poultry Sci. 17:77.

Moxon, A.L. and M. Rhian. 1943. Selenium poisoning. Physiological Rev. 23:305.

Moxon, A.L., M.A. Rhian, H.D. Anderson and O.E. Olson. 1944. Growth of steers on seleniferous range. J. Ani. Sci. 3:299.

Moxon, A.L. and A.E. Schaefer. 1940. Decomposition of selenium-cystine in electrodialysis and acid hydrolysis. So. Dak. Acad. Sci. 20:28.

Moxon, A.L., A.E. Schaefer, H.A. Lardy, K.P. DuBois and O.E. Olson. 1940. Increasing the rate of excretion of selenium from selenized animals by the administration of bromobenzene. J. Biol. Chem. 132:785.

Moxon, A.L., W.V. Searight, O.E. Olson and L.L. Sisson. 1944. Arsenic content of South Dakota cretaceous formations. So. Dak. Acad. Sci. 24:68.

Moxon, A.L. and W.O. Wilson. 1944. Selenium-arsenic antagonism in poultry. Poultry Sci. 23:149.

Olson, O.E., D.F. Jornlin and A.L. Moxon. 1942. The selenium content of vegetation and the mapping of seleniferous soils. J. Am. Soc. Agron. 34:607.

Olson, O.E. and A.L. Moxon. 1939. The availability, to crop plants, of different forms of selenium in the soil. Soil Sci. 47:305.

Olson, O.E., L.L. Sisson and A.L. Moxon. 1940. Absorption of selenium and arsenic by plants from soils under natural conditions. Soil Sci. 50:115.

Olson, O.E., E.I. Whitehead and A.L. Moxon. 1942. Occurrence of soluble selenium in soils and its availability to plants. Soil Sci. 54:47.

Painter, E.P. and K.W. Franke. 1935. Selenium in proteins from toxic foodstuffs. III. The removal of selenium from toxic protein hydrolysates. J. Biol. Chem. 111:643.

Palmer, I.S., O.E. Olson, A.W. Halverson, R. Miller and C. Smith. 1980. Isolation of factors in linseed oil meal protective against chronic selenosis in rats. J. Nutr. 110:145.

Petersen, D.F., H.L. Klug, R.D. Harshfield and A.L. Moxon. 1950. The effect of arsenic on selenium metabolism in rats. So. Dak. Acad. Sci. 29:123.

Petersen, D.F. and A.L. Moxon. 1951. Preliminary studies on the effect of ACTH in selenium intoxication. So. Dak. Acad. Sci. 30:Abst.

Poley, W.E. and A.L. Moxon. 1938. Tolerance levels of seleniferous grains in laying rations. Poultry Sci. 17:72.

Poley, W.E., A.L. Moxon and K.W. Franke. 1937. Further studies of the effects of selenium poisoning on hatchability. Poultry Sci. 16:219.

Poley, W.E., W.O. Wilson, A.L. Moxon and J.B. Taylor. 1941. The effect of selenized grains on the rate of growth in chicks. Poultry Sci. 20:171.

Potter, R.L., K.P. DuBois and A.L. Moxon. 1939. A comparative study of liver glycogen values of control, selenium and selenium-arsenic rats. So. Dak. Acad. Sci. 19:99.

Rhian, M. and A.L. Moxon. 1943. Chronic selenium poisoning in dogs and its prevention by arsenic. J. Pharmacol. Exp. Therap. 78:249.

Robinson, W.O. 1933. Determination of selenium in wheat and soils. J. Assoc. Offic. Agri. Chem. 16:423.

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