Document xznr5b60oKo12zgQMBNY6ZKbG

D. E. Carter and Quintus Fernando University of Arizona Tucson, AZ 85721 Part II. Metal Toxicity Evolutionary processes have selected certain elements, known as essential elements, to perform one or more physio logical functions and have rejected the other elements. Of the twenty six elenvents that are considered to be essential for life, the eleven elements, H, C, N, 0, Na, Mg, S, Cl, K, Ca, and P are major elements and the remaining fifteen, B, F, Si, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Se, Mo, Sn, and I are trace elements. Boron is essential for plant life, and ..recently the trace ele ments F, Si, V, Ni, and Sn have been shown to be essential or at least beneficial when included' in the diets of laboratory animals. It is possible that some of these trace elements may prove to be essential or beneficial to man. In addition to the essential elements, there are about thirty elements that are found in low concentrations in living systems. These are the inert elements for which no essential physiological functions' have been found, and their presence in the living organisms is probably caused by contact with the environment. The toxicity of the elements roughly parallels their abun dance in the earth's crust and in sea water. Elements that are present in low concentrations in nature are normally toxic. The metals Pb, Cd, and Hg are not very abundant in nature and have prominent toxic properties. The concentration of Pb is less than 10 ppm in the earth's crust and less than 0,03 ppb in sea water; the concentrations of Cd and.Hg are less than 0.2 ppm in the earth's crust and less than 0.1 ppb in sea water (30). The known essential trace metals in man are grouped to gether from vanadium through zinc in the first transition series in the periodic table. Molybdenum and selenium should be included in this group of essential metals although selenium is a non-metal rather than a metal. The concentrations of the essential metals as well as many of the inert metals in the human body are maintained at levels that are approximately constant by homeostatic mechanisms (Fig. 1). The concen tration of the essential trace metal has to be greater than the value at A for any effect, such as growth, to be manifest. At concentrations less than C, there is a deficiency of the essential trace metal and toxic symptoms may become evident. The measured effect shows a continuous increase with concen tration until the plateau BE is reached. It is at this plateau that the homeostatic mechanism operates fully. When the D. E. Carter, Associate Professor of Toxicology, has a joint appointment in the f Department of Pharmacology, College of tv Medicine, University of Arizona. He is also the Associate Director of the Toxi cology Program. His research interests are primarily in the areas of pharmacokinet ics and metabolism of drugs and toxins- Quintus Fernando, Professor of Chemistry, has a joint appointment as Professor of Toxicology and Forensic Sciences in the Toxicology Program at the University of Arizona. His main research interests are in the general area of metal complexation and trace metal analysis. 490 / Journal of Chemical Education jL l Figure 1. Illustration of the effect of the concentration of a trace metal on growth concentration: A, ito growth; C, maximum biological activity.; D, toxicity; A, lethality. Figure 2. Illustration of the effect of the concentration of a trace metal with no known biological function A. Very toxic metals (Cd, Hg, Pb); B. moderately toxic metals (As, Sb); and C, slightly toxic metals (At). concentration of the essential trace metal is increased from C to D, there is no increase in the measured effect and the excess metal is excreted. If the metal concentration is in creased beyond D, the metal becomes toxic as shown by a decrease in the measured effect, and at the concentration F where there is a vertical drop in the effect, the concentration of the metal has reached its lethal value. The curve, which is applicable to all living things, is quite wide for mammals but very narrow for certain bacteria and marine organisms (31, 32). It is evident, therefore, that exposures to low levels of es sential metals will not result in toxicity because there is no accumulation of these metals with age. On the other hand, exposure to very low levels ofCd, Hg, Pb, Sb, and Sn may have a cumulative effect and the human body burdens of t hese el ements that have no apparent biological function will increase since there are no homeostatic mechanisms that can operate to regulate the levels of these toxic metals (Fig. 2). More than half the elements in the periodic table are metals that have some degree of economic importance and are pro cessed industrially in quantities varying from many millions of tons to a fewounces per year. The use of metals in modern DUP040007924 The toxicity ofthe elements roughly parallels theirabundance in the earth's erust and in sea water. Elements that are present in low concentrations in nature are normally toxic. technology will continue to increase and, as a consequence, their concentrations in the environment will also increase. In the course of industrial activity, metals are released into the environment in several forms: water soluble species or inso luble precipitates that contaminate the rivers and lakes, metal-containing particulates and volatile metal compounds that contaminate the atmosphere. The total population is exposed to varying levels of these metal-containing contam inants. Industrial workers are exposed to metal fumes, metal oxide particulates, and volatile metal compounds on a daily basis at much higher levels than the urban population which is exposed to lower levels of toxic metal compounds, but on a continuing basis. Common methods of entry of these toxic metals into the human system is by inhalation or ingestion. Entry of toxic metal compounds into the body via skin expo sure is relatively commonplace for workers in many types of industry. From the results that have been accumulated over many years, a list of "safe or acceptable" levels of occupational exposure to toxic metals has been published in the Federal Register (33). These levels are assumed to be safe for expo sures ofeight hours duration that a worker may be Subjected to every working day. The volatile organometallic compounds are much more toxic than the relatively nonvolatile inorganic compounds or the metal itself, and quite often the route of entry of volatile compounds is via the skin in addition to the more obvious route of entry via the lung. It is difficult to assess the effects of continuous rather than intermittent exposure to metals or metal compounds that are present in the environment at lower levels than the "safe or acceptable" levels published in the Federal Register (33). After much debate the standard for airborne lead has been finally set by the Environmental Protection Agency at a quarterly average of 1.5 ng/m:*. Careful, long-term epidemiological studies can help eluci date the health hazards that are associated with exposure to mercury from the combustion of coal, or lead .halides that are produced in automobile exhaust gases. It is unfortunate that the results of many epidemiological studies cannot be inter preted unequivocally. Evidence from such studies has indi' cated that industrial workers who are exposed to arsenic have a high incidence of skin cancer and cancer of the respiratory, tract. This conclusion could not be substantiated by the res ults that were obtained with experimental animals (34). Metals are not biodegradable; the non-essential metals react to varying extents and tend to concentrate in the body thus increasing the total body burden. Exposures to extremely low levels of environmental metal contaminants over long periods can, therefore, cause subtle health effects, which in some in stances mimic chronic diseases. Tittle is known about this form of metal toxicity and the adverse health effects that are caused are almost impossible to predict (31). The Essential Trace Metals All the trace metals that are considered to be essential belong to the first transition series, except selenium and mo lybdenum. There are some indications that vanadium is an essential element in certain biological systems (35, 36). Chromium (III) is essential for glucose and lipid metabolism (37). Manganese (II) is a cofactor in a number of enzymatic reactions. Although enzymes such as cytochrome and xanthine oxidase contain iroft. its major role is in the formation .of he moglobin; Cobalt (if) is a component of vitamin Bja which is essential for the prevention of anemia. Nickel (11), however, is probably an essential element for mammals, but no bio logical function has been demonstrated for this metal. Cijppei and zinc are both essential metals and play tut important rolein enzyme activity. Copper is required by oxidative enzymes such as catalase and peroxidase and zinc is u constituent of a variety of enzymes including carbonic anhydra.se, earboXypeptidase, and alkaline phosphatase. Molybdenum is an es sential element that is widely distributed in nature and rndy be found in.a number of oxidation states. It is a cofuetor for xanthine oxidase and aldehyde oxidase. The biochemical role of selenium is not well understood although it is considered to be an essential element. The normal levels ofall the essential elements in the human body are maintained by homeostatic mechanisms. The esti mated daily intake of these elements via food or drinking water together with their human body burdens are given in the table (38). The toxic action of most of these elements is. therefore, largely confined to the respiratory tract as a result of chronic or acute occupational exposures, unless, of course, a large quantity of one of the compounds of these elemen ts is ingested accidentally. Vanadium and Chromium Vanadium exists in a number of oxidation states the com monest of which are the -fill and +V states.it is ubiquitous in nature and is found in many foods, particularly fats and oils. When any vanadium-containing compounds are ingested, they are absorbed only moderately; the total body burden is maintained at an approximately constant value by homeo stasis, the principal route of excretion being via the kidney. Only a small percentage, however, ofany inhaled %'anadium Compound is excreted in the urine, and therefore, vanadium compounds tend to accumulate in the lung. 'Hie occurrence of bronchitis and .bronchopneumonia is more frequent in Workers who have been exposed to dusts containing vanadium pentox'ide. Vanadium occurs widely in fuel oil especially if it is of South American origin. The combustion of fuel oil in power plants and other Industrial operations releases vana dium oxides into the atmosphere and can capse an environ mental hazard. The seriousness of this hazard may be gauged from the following Observations: vanadium pent oxide is recovered from flue dusts; urban air contains 0.05 gg V/nv' (39); vanadium may exert a synergistic effect on cadmium in causing heart disease (40). The essential role of chromium, unlike that of vanadium, has been| established. Although ull the oxidation states of chromium between +11 and +Vl are known, the stable ox-i- Estimated Daily Intake and Human Body Burden of the Essential Trace Elements Daily intake (mg) Human body burden (mg/70 kg) V 2.5 30 Cr 0.06 <6 Mn 5 20 Fe 15 4100 Element Co Ni* 0.03. 0.45 t <10 Cu 3.2 100 Zn 12 2300 So Mo 0.060.15 ' 15 0.35 9 " Probably an essential element 1| Volume 56. Number 8. August fiRy^i0.07925 dation states in aqueous solution are the -4-III and the +VI states. Only the +III state of chromium plays an essential role in certain metabolic processes and any chromium that is in gested in the +VI state is irreversibly reduced in the body to the +III state. The average daily intake of chromium com pounds that occur in food and in drinking water is about 60 fig ofwhich only one percent is absorbed to maintain the total body burden Viable 1). The volatile organometallic compounds are much more toxic than the relatively nonvol atile inorganic compounds... The concentration of chromium, like that of vanadium, in the lung increases with age and implies that inhaled atmo spheric particulates contain an insoluble form of chromium. It has been suspected for some time that long term exposures to insoluble chromium (VI) compounds can cause lung cancer {41, 42). Soluble as well as insoluble chromium (VI) com pounds are released into the atmosphere as welding-fumes during the welding of chromium-bearing alloys. The Occu pational Safety and Health Administration (OSHA) has proposed an airborne limit of 1 ftg/m3 of chromium (VI) compounds which are probably carcinogenic and 25 jug/m3 of non-carcinogenic chromium compounds which are presu mably the water soluble sodium and potassium chromates. It is difficult to estimate a "safe" level of chromium that would not be hazardous in the environment, especially if the chro mium is present as insoluble chromium (VI) compounds. The reported presence of about 0.02 fig/m3 of chromium in urban air should, therefore, be of some concern (38). Manganese and Iron Manganese and iron are both essential elements--the av erage body burden is about 20 mg of Mn and 4 g of Fe. In gested manganese is excreted via the bile and is regulated efficiently by a homeostatic mechanism that maintains a constant level of manganese in tissues (43). The homeostatic mechanism for limiting the absorption of iron involves the oxidation of iron (II) to iron (III) in the mucosa of the gas trointestinal tract, The accidental ingestion of a large quantity of FeSO-t tablets or oral iron preparations can result in acute toxicity that is due to the irritation of the gastrointestinal tract. The excessive ingestion of. iron over a long period can lead to hemosiderosis, a condition in which the iron content in all body tissues is high. The average concentration of manganese in urban air is 0.10 fig/m3 and of iron is 1.58 figfxn3. The lungs do not accumulate manganese and long term exposures to significant airborne concentrations of manganese are.not considered to be a .health hazard. Acute exposures, however, to manganese dioxide dusts in industrial atmospheres can cause respiratory problems. Chronic occupational exposures to manganese dioxide dusts for two years or more can have serious consequences. It has been reported that the central nervous system is affected by chronic manganese poisoning and the resulting symptoms and degenerative changes resemble Parkinson's disease (44). No significant physiological changes are caused by chronic in halation exposure to iron oxide dust; the mottling of the lung or siderosis is considered.to be benign (45). Hematite miners, however, have a significantly higher death rate due to lung cancer, but this may be attributed to the radioactivity that has been observed in some of the hematite mines (46). Cobalt Of the remaining elements in the first transition series, cobalt is a relatively rarebut essential element; nickel has no known essential human biologica} l; function; copper and zinc, 492 / Journal of Chemical Education both essential elements,.are widely distributed in nature and are found in all living organisms. Chronic oral administration of high levels of cobalt com pounds can cause goiter (35), and an acute industrial exposure to ~2 mg/nv' can lead to respiratory problems. No systemic toxicity has been attributed to nickel compounds except to the carbonyl, NiCCOh, which is extremely toxic--an exposure to 30 ppm for 30 min is lethal (47). Chronic exposure to nickel carbonyl can cause cancer of the lungs in experimental animals and has been implicated in the occurrence of lung cancer in humans. In view of the reported presence of nickel carbonyl in cigarette smoke (48), prolonged exposure to cigarette smoke in confined spaces should be considered to be a Serious envi ronmental hazard. Copper. The range of copper, between deficiency and toxiciiy (plateau BE in Fig, 1), in man is quite wide, but for many or ganisms it is rather narrow. In man, the intestinal mucosa acts as a barrier to the unrestricted absorption of ingested copper.; in most mammals, including man, there is a well-developed mechanism for copper homeostasis, for the bile is the primary;, excretory route. Other organisms do not have effective barriers against the absorption of ingested copper. Although industrial exposure to copper compounds does not result in acute or chronic poisoning, brass workers exposed to metal fume can contract "metal fume fever". Work with experimental animals has given some inditmion of the problems that may arise with the use of copper-containing intrauterine devices (49). The mode of action of copper in these IUD's is not well understood. It has been demonstrated that the copper metal in the lUD's dissolves at the rate of about 25gg per day with the concom itant formation of hydroxyl radicals and the potential prob lems that may arise with the use of copper-containing iUD's have been summarized (50). Zinc The toxicity of zinc is obscured by the inevitable presence of cadmium in zinc compounds. Hence, the zinc:cadmium ratio is of considerable importance in understanding the effect ofzinc on living organisms (51,52). Acute industrial exposure to freshly formed zinc oxide particulates in the respirable range (<1 jam in diameter) results in metal-fume fever. If flocculation of the zinc oxide occurs, the particulates increase in size and, therefore, do not penetrate deeply into the lungs. There are no chronic effects that are caused by the inhalation of zinc oxide (53). Selenium and Molybdenum Selenium, a Group VI element, forms compounds with co valent bonds and has formal oxidation states of +IV and 4-VI. In contrast to the rest of the essential trace elements which are metals, selenium is a non-metal; its biochemical role has not been completely elucidated. Selenium compounds are ingested from food and water and the total body burden is estimated to be about 15 mg/70 kg. Selenium compounds are also present in urban air, presumably as a result of the same type of industrial activity that releases sulfur compounds into the atmosphere. The body has a homeostatic mechanism that retains trace levels of selenium, the excess being excreted primarily (n the urine (54). A selenium concentration of more than 15 pg/100 ml in the Urine is indicative of excessive ex posure to selenium compounds. Hydrogen selenide, H->Se, and selenium oxychloride, SeOCla, are extremely hazardous compounds that may be encountered in chemical industry. In experimental animals, exposure to 10 ppm of H^Se is fatal and 0.01 ml of SeOCl, applied dermally is fatal. Acute exposure to selenium com pounds affects the central nervous system and chronic inha lation exposure produces a variety ofsymptoms including the well-known symptom of garlic breath that is caused by di methyl selenide present in exhaled air (54). DUP040007926 One of the commonly encountered toxic gases in the labo ratory is hydrogen sulfide,.HoS, which has a paralyzing effect on t he central nervous system as well as the olfactory system. Exposure to 600 ppm of H.S for 30 min is fatal as a result of respiratory failure- The mechanism of toxicity of selenium-containing com pounds is still under discussion, one of the open questions being whether the conclusions that are deduced from animal experiments are applicable ttvman. The extensive toxicological studies that have been carried out with selenium compounds have uncovered some interesting, but complex, interrela tionships among certain elements that exhibit various types of toxicity. For example, arsenic, mercury, and thallium were found to inhibit the pulmonary excretion of dimethyl selenide but only arsenic lowered the concentration of selenium in tissues and prevented liver damage (55,55). Another factor that cannot .he ignored is the observation that the oxidation states of all these elements govern their degree oftoxicity and also affect their inhibitory action. The importance of the re lationship of the oxidation state and biological function is much more striking in the case of molybdenum which is an essential trace element and a member of the second transition series. In experimental animals, large doses of the stable molybdenum sulfide, MoSo, did not show any injurious effects, whereas, molybdenum (VI) compounds were much more toxic. The toxicity of molybdenum compounds is influenced by the presence of other metals. For example, copper antagonizes the absorption of molybdenum (VI) compounds from food. It is of interest that there are no data on either acute or chronic toxic effects ofmolybdenum compounds as a result of indus trial exposure despite the rather wide use of molybdenum in industry. The Toxic Metals The trace metals and their compounds that have been considered so far are essential to one or more types of living organisms. The rest of the elements are either inert and do not ,... the routeofentry of volatile compounds is via the skin in addition to the more obvious route ofentry via the lung* accumulate in the body or are toxic and have long biological half lives. Among the more toxic elements are beryllium, cadmium, lead, and mercury, as well as their compounds. Beryllium was considered to be' a severe industrial hazard when it was widely used in the manufacture of fluorescent lights and neon signs. Inhalation of'beryllium-containing dusts results in chronic pulmonary granulomatosis (57). Arsenic is a non-metal which is widely distributed in the biosphere. It is present in air near coal-burning power plants, smelters and refineries, in drinking water supplies and in the soil. In general, arsenic occurs in the +V oxidation state in nature, but it is introduced into the environment in the +III state as a result of industrial activity. The +V state is less toxic than the +III state which has a tendency to be oxidized in the body to the +V state. The arsenic content of human hair and nails has been used as a diagnostic test for arsenic poisoning (58,59). There is epidemiological'evidence that implicates industrial exposure to arsenic compounds in cancer of the skin and res piratory tract. A high arsenic concentration in drinking water has been linked to an increased susceptibility to skin cancer (60). Modern day industrial exposures are confined to the processing of tin, zinc, and lead in which the major toxic agent is arsine, As Hm, a gas with a garlic-like odor. As little as 10 ppm of this gas can be fatal. Cadmium The acute toxicity of cadmium has been known for about a century, but it was only 25 years ago that the chronic toxic effects of cadmium were recognized. In the 1940's, during the manufacture of alkaline nickel-cadmium batteries in Sweden, a number ofdeaths occurred. The causative agent wh ich was not known at tjiat time was cadmium oxide, and its concen tration in the air was estimated to be several milligrams/m3 (60). The present threshold for cadmium oxide dust is 0.2 mg/m3 and for cadmium fume is 0.1 mg/m3; both these threshold values are probably much too high. In Fuchu in the Toyama prefecture in japan, a crippling and painful disease, itai itai byo, was related causally to chronic cadmium poisoning and was first seen in post-meno pausal women who had histories of several pregnancies. The ingestion ofrice grown infields that were irrigated with cadmium-contiiminated water resulted in the daily intake of about 300 fig of cadmium. The prolonged ingestion of high levels of cadmium resulted in severe renal dysfunction ao compan'ied'by increased excretion of protein, glucose, aifilnoacids, ah'd phosphorus. The low intake of calcium and vi tamin D wfere additional factors that caused the osteomalacia or itai itai disease. The severe pain that was experienced by the victims of this disease was attributed to fractures of soft ened bones (63). In the United States, the average daily intake;, of cadmium from food is about 50 fig and about 10 Mg from : water that has passed through galvanized pipes. Approxi mately six to ten percent of the ingested cadmium is absorbed. In biological systems, the cadmium:zinc ratio hasan important bearing on the absorption, excretion and ultimately the tox icity of cadmium. There are very small amounts of cadmium in the atmo sphere, and it is estimated that about 0.02 fig of cadmium may be inhaled daily. Cigarette smoke contributes a significant amount--approximately 0.1 fig of cadmium is inhaled from the mainstream of each cigarette, but the sidestream smoke contains a much higher concentration of cadmium (64). About ten percent of the inhaled cadmium is retained in the lungand several factors, such as size of the particulates and their so lubility, govern the percentage of cadmium retained. Chronic inhalation exposure to cadmium can result in proteinuria and emphysema. Acute industrial exposure can affect the pul monary and cardiovascular systems without necessarily af fecting the kidney which is the primary target organ in.cadmium poisoning. Exposure to cadmium compounds is a serious occupational hazard as well as a potential hazard to the general population. Although ho overt health problems due to cadmium ingestion have been found in the United States, the prolonged ingestion of cadmium from food and water can have serious conse quences. Lead Lead ista highly toxic and cumulative poison. It has been recognized as an industrial hazard for many years, but its long-term effects as an environmental hazard have become more important especially in the highly urbanized areas. The atmospheric concentration of lead in urban areas range from 0,4 to 7.6 jng/m3 (65). In heavy automobile traffic, this lead concentration can be as high as 38 fig/m3 from the combustion of gasoline containing lead alkyl additives. The daily intake otl lead from food and water is, however, much greater than that from, the inhalation of lead-containing particulates (66). The average concentration of lead in the water supply in the United States cities is about 60 fig/l. This value can increase considerably if lead pipes or pipes with lead joints are Used in carrying the water supply. The average daily intake of lead from food and beverages varies widely, but a: reasonable es timate is about 300 Mg/day of which about five to ten percent is absorbed. Once absorbed, the lead tends toaccunutlate in the bones which have been found to contain over 90 percent of the total human body burden of lend (120 mg pb/70 kg). The primary routes of lead excretion is via the urine and feces; both routes reduce the lead burden by approximately the same amount. The average lead content in urine is 35 Volume 56. Numbers, August ,3,0UP040007927 Metals arc not biodegradable;the non-essential metals react to varying ex tents and tend to concentrate in the body thns increasing the total body burden. p{r/100 ml, and a urinary level .of 150 Mg/100 ml is indicative of a hazardous exposure to lead (67). There is a correlation between the concentrations of lead and aminolevulinic acid in urine, and the determination of urinary levels of this com pound has been suggested as a screening procedure for the early detection of lead exposure in children (68, 69). It has been shown, however, that erythrocyte 5-arninolevulinic acid dehydrase is more sensitive than aminolevulinic acid in urine as an indicator of lead levels in blood, especially at low lead levels (<40 jug/ml) (70). Chronic lead poisoning is characterized by neurological problems, renal tubular dysfunction and anemia. Children have a lower lead tolerance than adults and damage to the central nervous system resulting in lead encephalopathy and lead neuropathy is a common occurrence among children who have had a chronic exposure to lead, probably by the ingestion of lead-containing paints. The. mechanism by which lead im pairs the central nervous system is not known. Volatile organic lead compounds are absorbed through the skin, the gastrointestinal tract, and the lungs, and affect the central nervous system. Tetraethyl lead is one of the com monest organic lead compounds that has been produced for many years industrially as an antiknock additive for gasoline. The decrease in the production of this volatile and highly toxic organic lead compound will reduce the importance of lead as an industrial hazard and also decrease the total burden of lead in the environment. Tolerance to lead is influenced by a number of factors and the establishment of a maximum long-term "safe" level will depend on the factors that continue to be operative over the long term. For this reason, a threshold value at which an ad verse health effect is observable cannot be determined with any degree of certainty. The World Health Organization has given a provisional tolerable weekly intake of lead by an adult man as 0.05 mg/kg body weight (71). This level does not, of course, apply to infants or to children. Mercury Elementary mercury is used widely in industry in the electrolytic production of chlorine and sodium hydroxide. Phenyl mercury is used in the paper and pulp industry and other mercurials also are used as fungicides. All these uses Contribute to the pollution of the environment and can lead to occupational as well as environmental hazards. The chemical form of mercury to which industrial workers or the general population is exposed has an extremely'important bearing on the toxicity of mercury. Mercury compounds or elemental mercury inhaled from the air is negligible compared with the intake from food, ex cept in instances where there is an environmental hazard. Mercury poisoning has been reported among goldsmiths, and workers in the fur and felt hat industry in which mercuric nitrate was used in the treatment of furs. A recent survey showed that in many chemistry laboratories, as well as other university laboratories, the mercury level exceeded 0.005 mg/m3 which is the maximum allowable concentration in the United States (72). Exposure -to elemental mercury vapor affects the central nervous system and causes characteristic psychic and emotional disturbances. In general, these effects are reversible especially if the exposures are subacute. The toxicity of mercury vapor is highly species dependent, and, therefore, it is not possible to extrapolate the results of animal studies to man. |' Exposure to mercurous or percuric compounds, such as HgaCri or HgCl2, leads to accumulation of mercury in the 4$4 l Journal of Chemical Education kidney which is the primary target organ; there is little effect on the central nervous system. Aryl mercury and alkoxyalkyl mercury compounds, for example, CfiH5HgCl and CHaOCHzHgCl, are converted into mercuric ions in mam malian tissues and their toxicity resembles that of mercuric compounds (73). The biotransformatipn of mercury into short chain alkyl mercury .compounds, for example, CH;)HgCl, by bacteria has posed a toxicological problem of great importance (74}: As with elemental mercury vapor, the toxicity of methylmercury is species dependent, and the applicability of the results of animal studies to man remains questionable. Two episodes of acute: methylmercury poisoning with disastrous conse quences have been documented. In japan, mercury-containing factory wastes were discharged into the Minamata Bay, The consumption of fish containing high concentrations of methylmercury resulted in an outbreak of methylmercury poisoning which was characterized by a high incidence of "congenitally defective" infants. The methylmercury can pass the placental barrier and can concentrate preferentially in fetal tissues and the brain resulting in mental deterioration, cerebral palsy, arid mortality (75). A more recent outbreak of methylmercury poisoning occurred in Iraq and was caused by the ingestion of bread made from wheat that was treated with a methylmercury fungicide. The toxic symptoms thatinduded constriction of the visual field, slurred speech, and hearing difficulties appeared about two months after ingestion of the contaminated bread (76). A comparison of the group that was briefly exposed in Iraq with a group that is being subjected to a long-term low level exposure to methylmercury in Samoa indicates that sensitivity to methylmercury depends on age and that, the maximum body burden is more important than the length of exposure in determining the response to meth ylmercury (77), A provisional tolerable value for the intake of mercury from food hasbeen established (78). The weekly intake should be 0.3 mg rig per person of which not more than 0.2 mg should be present as the methylmercury ion, CH$Hg1'. Extraneous factors,guch as age and pregnancy have been taken into ac count ip establishing these values. Another factor that is of interest is that selenium compounds can counteract the tox icity of both inorganic and organic mercury compounds. The selenium content of the diet may, therefore, afford some protection to the toxic effects of methylmercury (79). All compounds including trace metals are toxic if they are ingested,or inhaled in sufficiently large quantities over long periods (Figs. 1 and 2). The justification for the classification of metals such as Pb, Cd, and Hg as toxic metals is that they have nojapparent biological function and their toxic properties have been recognized for decades. There are several trace el ements that may have a bearing on human health especially if patterns ofindustrial activity undergo changes in the future. For instance, antimony and bismuth are low level pollutants that havC been measured in urban air (30). Common bismuth compounds that are either ingested or inhaled are not hazar dous. Antimony compounds can generate stibine, SbH;*, under reducing conditions and may be involved together with AsHs as a serious industrial hazard. The t<)xic actions of trace metals are not confined to the activity of a single metal in the absence of all other metals. It is not surprising, therefore, that the maximum tolerances of trace metals are influenced by the presence of other metal ions. Well-known examples are the reversal of the adverse effects of cadmium by the administration of zinc compounds and the protective action ofselenium against the toxicity of ,r DUP040007928 both inorganic and organic mercury compounds in animals and perhaps in man. Throughout this discussion of the toxicity of metals, very few specific references have been made to the oxidation state of the met al species that gives rise to toxicity. Much work re mains to be carried out in this area and until detailed mech anisms of the toxic action of metal-containing species have been elucidated, only qualitative generalizations concerning oxidation state can be made. Metal toxicity is caused by the metal itself or volatile compounds of the metal that are either inhaled or absorbed through the skin, for example, Bg vapor, Ni(CO),| and (CH;,).,Pb. More commonly, insoluble or partially soluble metal compounds are either inhaled or ingested, and it has been tacitly assumed that the toxic action of the metal is at tributable to the metal ion in one of its oxidation states. This is, of course, an oversimplification. The metal ion is bound by monodentate ligands, for example, Cl-, bidentate ligands, for example, amino acids or even multidentate ligands such as enzymes. The metal containing species to which the toxic action can be attributed has not been identified in the vast majority of eases, and the identification of the species that triggers the toxic action is one of the most challenging prob lems in the field of chemical toxicology. Literature Cited *30) Beltlos, R. P,, 'Toxicology: The Basic Science ofPoisons," {Editors; CasareU.L. <J., and Doull, J. D.1, Macmjilan Inc., New York, 1975. <31 V Sehroedcr. H. A- "Recondite Toxicity oi Trace Elements." in "Essays in Toxicology, Vl. 4," (Ktfitor: Hayes. W. Academic Prcss.New 'York, 1973. 132) VenchOsov, A. 1., "Trace Element Metabolism in Animals." {Editor: Hoekstra.W.G., el al.), University Park Press, Baltimore. Md., 1974, Vdf. 2. 133) Federal Rcgwter, 3fi No, 157, Friday. August 13.11971). f.M) Byron. \Y. R.,Brouver,J. B., and Hansen, \Y. H., Toxical, and Appl. Pharmacol., 16, ` 132 <1967). t;lf) Browning. E., "Toxicity of Industrial Metals." 2nd Ed.. Butterworths, London, 1969. (36) Schwat z. 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R.,and 2eleako, V,, Nature, 254,238,0975). 4" VivUiott <y CHEMICAL EDUCATION Society Hospitality Lounge The Hospitality Lounge was an innovation at the National meeting in Honolulu, an appropriate occasion because of the international nature of the meeting. This was borne out by our visitors who were from .Japan, Australia, Canada, England, Puerto Rico, as well as most of the United States. About fifty people a day stopped in, staying anywhere from a few minutes to an hour or two. In addition to a hard core of college and university professors, there were high school teachers, students, post-docs, deans, research ^hemists, historians, and even a photographer. ; The Lounge became an oasis,in the midst of the meeting. It was a p!acb: toenjoy the view of the yacht harbor and the Pacific from a balcony on the 12th floor of the Ilikai; to have acup of coffee of a drink of orange juice, sit down, and rest your feet for a few minutes; to go off in a quiet corner to review a talk; to, meet nevf beople, obtain information about the Division and its activities, join the Division or subscribe to the Journal; to have national or international committee and subcommittee meetings off in a corner or on a balcony (the Division of History of Chemistry even held its executive committee meeting in our Hospitality Lounge!); to stow all manner of parcels, packages, briefcases, suitcases, A/V equipment and other im pedimenta for a few minutes or all day; to look through 1920's issues of the Journal, photographs of past biennial meetings, a complete collection of ACS standardized tests, or information on chemistry programs in other countries; to enter the daily raffle for a free sidwcription (or extension) to J. Chcm. Educ, to use the phone, to feel at home, to exchange ideas, to learn a little Japanese, to make plans for future meetings. Many persons thought the Hospitality Lounge was a successful experiment, so successful that another is planned for the Washington meeting. Many of the features which characterized Honolulu will be used again, including a daily raffle. It will be in the same hotel as the Chcm. Iiduc. sessions; we do not have the-hotcl name or room number at the early elate at which t his is being written, but we wilHtavc signs posted around the meeting area. Look for them. See you there! John ami llotty Moore Eastern Michigan University Hob ami Corinm* Hrnsted The University of Minnesota Volume 56, Number 8, August WDUP040007929