13 Mercury Thomas W. Clarkson University of Rochester School of Medicine, Rochester, New York 1. INTRODUCTION Several major reviews were useful in the preparation of this review (1–8). 1.1 The Physical and Chemical Forms of Mercury The element mercury is aptly named after the messenger of the Roman gods, as it is the most mobile of all the metals. In its ground or zero-oxidation state (Hg 0 ), mercury is the only metal that is liquid at room temperature. Liquid metallic mercury can form stable amalgams with a number of other metals. An amalgam with silver and copper is the basis of dental amalgam tooth fillings. Both the amalgam and liquid phases allow mercury to vaporize as a monatomic gas (usu- ally referred to as mercury vapor). Mercury has two oxidation states each capable of forming a variety of chemical compounds. In the mercurous state, two atoms of mercury, each having lost one electron, form the mercurous ion (Hg-Hg ϩϩ ). Mercuric mercury (Hg ϩϩ ), where two electrons have been lost from one atom of the metal, forms most of the compounds of mercury. Mercuric mercury can also form a number of ‘‘organic mercury’’ com- pounds by bonding to a carbon atom, for example, the phenyl (C 65 -Hg ϩ ) and methyl (CH 3 -Hg ϩ ) mercuric cations. Methyl mercury compounds, used exten- Copyright © 2002 Marcel Dekker, Inc. sively in the past as fungicides, have been responsible for several mass outbreaks of poisoning. 1.2 Sources of Human Exposure In the past, mercury and its compounds found a wide variety of uses in agricul- ture, industry and medicine. Studies of mercury levels in peat bog in northwest Spain indicate that substantial anthropogenic deposition took place as early as 2500 years ago. This, the authors (9) stated, coincided with the startup of the Almaden mercury mine in central Spain. The authors also concluded that anthro- pogenic mercury has dominated the deposition record in Spain since the Islamic period (8th–11th centuries, a.d.). Global emissions have increased in the past 100–150 years. Today, most human exposure to mercury vapor is in the occupational set- tings and from dental amalgam, and to methyl mercury in diets containing fish and seafood (5). A small amount of inorganic mercury of unknown origin is also present in the diet of the general population. Owing to the introduction, in recent years, of controls over the uses of mercury, occupational exposures have dimin- ished. They mainly involve industrial plants using liquid mercury as an electrode in the electrolysis of brine to produce chlorine and caustic soda (the chloralkali industry), the manufacture of thermometers and other scientific equipment, the production of fluorescent lights, the use of metallic mercury in the extraction and refining of gold and silver, and the use of amalgam fillings in dentistry. In fact, gold mining has become a major source of human exposure in many developing countries in recent years (10–12). Dental amalgams are the dominant source of exposure to mercury vapor in the general population. It was estimated that from 3 to 17 µg Hg/day was absorbedfromamalgams(Table1),farexceedingothersourcessuchastheambi- ent atmosphere. More recent reports are in general agreement with this estimated range. For example, Barrega ˚ rd et al. (13) found mercury levels in the kidney cortex taken from living kidney donors in the general Swedish population to be significantly higher (0.47 µg Hg/g wet wt) in people with amalgams as compared to those without amalgams (0.15 µg Hg/g wet wt). Kingman et al. (14), in a study of a large group (n ϭ 1127) of U.S. military personnel, found statistically significant correlations between amalgam exposure and urinary mercury concen- trations confirming previous reports. Unusually high intakes have been reported in a few individuals. Barrega ¨ rd et al. (15) reported on three amalgam-bearing individuals who attained urinary excretion rates of about 50 µg Hg/g creatinine in urine. This urinary excretion rate corresponds to a steady daily intake of over 80 µg Hg, perhaps as high as 160 µg Hg. In the case of these individuals, the long-term use of chewing gum may explain the extreme values as chewing accel- erates the release of vapor from amalgams. They estimated that about one in Copyright © 2002 Marcel Dekker, Inc. T ABLE 1 Average Daily Intakes in Adults in the General Population of Mercury and Its Compounds Inorganic Methyl Source of Mercury mercury mercury exposure vapor compounds compounds Air 0.03 (0.02) 0.002 (0.0001) 0.008 (0.006) Drinking water 0 0.05 (0.0025) 0 Food Fish 0 0.6 (0.04) 2.4 (2.3) a Nonfish 0 3.6 (0.25) 0 Dental amalgam 3.8–21 (3–17) 0 0 a Daily intakes are much higher in populations depending on seafood or freshwater fish as the major protein source. Source: Adapted from refs. 4.5. 2000–10,000 persons in the general population in Sweden may attain urine levels of 50 µg H/g creatinine. These values are at about the threshold limit for adverse effects due to occupational exposures to mercury vapor. Given the worldwide use of amalgam, such estimates indicate that large numbers of people could have such values. Environmental exposures are mainly to methyl mercury compounds as a result of the biomethylation of inorganic mercury by microorganisms present in aquatic sediments and the subsequent bioaccumulation of methyl mercury in aquatic food chains. The ability to methylate mercury is found in some of the earliest evolutionary life forms such as the methanogenic bacteria. After release from the methylating microorganisms, methyl mercury ascends the aquatic food chain via zooplankton into fish. The highest concentrations of methyl mercury are found in edible tissues in long-lived carnivorous fish and sea mammals at the top of the food chain. Inorganic mercury that is the substrate for biomethylation may be naturally present in aquatic sediments or deposited via local pollution or widely distributed to bodies of fresh and ocean water though the global cycle (16). The global cy- cling of mercury involves natural sources such as the degassing of the earth’s crust releasing mercury vapor to the atmosphere. Anthropogenic sources include coal-burning power stations and waste incinerators. Mercury vapor is the princi- pal form of mobile mercury in the atmosphere. With a residence time of 1 year or so, it distributes globally from its source. The discovery of mercury in aerosols 19 km above the earth’s surface gives further evidence for the long residence time in the atmosphere (17). It is converted to a water-soluble form by processes that are not yet well understood and returned to the earth’s surface in rainwater. Copyright © 2002 Marcel Dekker, Inc. The global cycling of mercury is believed to be responsible for the transport and deposition of mercury in areas remote from the original source whether natural or anthropogenic. Mercury in the general atmosphere and in unpolluted drinking water is present in such low concentrations as not to amount to a significant source of human exposure (5). 2. DISPOSITION AND TOXIC ACTIONS Each of the major forms of mercury is characterized by a unique pattern of dispo- sition and toxicity, so each will be treated separately. 2.1 Liquid Metallic Mercury The occasional breakage of mercury thermometers in the mouth results in liquid mercury entering the gastrointestinal tract. It passes through virtually unabsorbed and unchanged to be excreted in the feces. No adverse effects of such accidents have been reported. Accidental breakage of Miller-Abbott tubes can release liquid mercury into the lungs where it can reside for many years. It is slowly oxidized to ionic mercury that passes into the bloodstream leading to elevated tissue levels. However, no adverse effects have been noted except for mild kidney damage (18). Indeed, in the early years of the nineteenth century, tablespoon quantities of the liquid metal were administered orally in attempts to relieve constipation. 2.2 Mercurous Mercury Since human exposure to compounds of mercurous mercury now occurs rarely if at all, we have little information on its disposition in the body. Compounds of mercurous mercury, especially the chloride salts, have a low solubility in water and are poorly absorbed from the gastrointestinal tract. In the presence of protein, the mercurous ion disproportionates to one atom of metallic mercury (Hg 0 ) and one of mercuric mercury (Hg ϩϩ ). Some of the latter will probably be absorbed into the bloodstream and distributed to tissues as discussed below. Mercurous chloride (calomel) was widely used medicinally in past centu- ries up to about the middle of the present century. It has a mild laxative action that probably explains why it was added to teething powers. However its medici- nal uses were stopped when Warkany and Hubbard (19) connected the childhood disease of acrodynia to presence of calomel in teething powders. This disease is characterized by the infant having pink cheeks and hands, being photophobic, and experiencing joint pain sufficiently severe to cause the child to cry and complain frequently. In fact, the constant crying by the child eventually led distraught mothers to seek medical attention. An interesting characteristic of the disease was that of about 1000 infants taking mercury-containing teething powder only Copyright © 2002 Marcel Dekker, Inc. one would develop the full-blown syndrome. The disease is reversible after cessa- tion of exposure and can be successfully treated by a mercury complexing agent such as British antilewisite (BAL). Since the discovery that inorganic mercury was the cause (19) cases are now extremely rare. The mechanism whereby mercury produces this disease is not known. Acrodynia can also be produced by exposure of children to other forms of mer- cury such as mercuric salts, phenyl mercury compounds, and inhaled mercury vapor. Since all these species of mercury can release mercuric mercury in the body, it seems likely that this form of mercury is the proximate toxic species. It is of interest that this disease has not been reported in adults or after exposure of children to methyl mercury in the diet or after placement of dental amalgam fillings. Mercuric mercury may also be responsible for the laxative action of mercurous compounds. 2.3 Mercuric Mercury 2.3.1 Disposition The diet is the main source of exposure of the general population. Experimental studies on human subjects indicate that on the average, 15% of an oral dose of mercuric mercury is absorbed whether given as ionic mercury or attached to protein. However, individuals differ considerably in the amount absorbed, rang- ing from 8% to 25% of the ingested dose (20). When administered in creams used to whiten the skin, some absorption of mercuric mercury must take place as severe systemic toxicity has occurred. Occupational exposure of the mercuric oxide aerosols can occur in the manufacture of mercury batteries and perhaps to mercuric chloride aerosols in the chloralkali industry. As with any aerosol, the retention and pattern of deposition in and degrees of absorption from the lungs will depend on particle size and solubility. Experiments on dogs inhaling mercu- ric oxide aerosols indicated substantial retention and subsequent distribution to body tissues (21). Studies on 10 adult volunteers (22) given a single nontoxic oral dose of mercury, either in the ionic form as mercuric nitrate or protein-bound, yielded important data on absorption, distribution, and excretion in humans. On the aver- age 15% (range 8–25%) of the oral dose was absorbed. The blood compartment contained an average of 0.27% (Ͻ0.07–0.48%) of the ingested dose 24 h later. Levels in plasma were about two and a half times of those in red blood cells. In six volunteers the biological half-time in plasma was 24 days (range 12–40) and in red cells, 28 days (range 13–42). The whole body half-time was longer, 45 days (range 32–60). According to animal data (18), about 30% of the body burden of inorganic mercury is found in the kidney with the highest levels in the corticomedullary region. A limited degree of penetration of the blood-brain barrier occurs but to a Copyright © 2002 Marcel Dekker, Inc. far lesser extent than what is seen for inhaled mercury vapor and methyl mercury compounds. Likewise mercuric mercury dose not cross the placenta to any sig- nificant extent but, instead, accumulates in placental tissues. Elimination from the body occurs predominantly via the urine and feces although some excretion in sweat may occur. Fecal excretion, at least in part, starts with secretion in bile, according to animal experiments (23,24). Mercuric mercury is secreted as a complex with glutathione via the glutathione transporter located in the cannicular membrane of the hepatocyte. This mechanism does not operate in suckling animals but switches on abruptly at the time of weaning. Glutathione conjugates (and perhaps conjugates of other small-molecular- weight thiols) of mercuric mercury may also be involved in kidney uptake and urinary excretion but a detailed mechanism is not yet available (25). Studies on animals with radioisotopes of mercury reveal that all the mercury in urine derives from mercury in kidney tissues as opposed to the filtration and excretion of mer- cury from the bloodstream (18). Information is limited on suitable biological monitoring media for mercuric mercury. Plasma should be a useful medium but would be confounded by simulta- neous exposure to mercury vapor. Whole blood or red blood cells are less suitable as dietary exposure to methyl mercury would affect the mercury levels. The rate of urinary excretion should reflect kidney levels. Correction for changes in uri- nary flow rates may be needed, as discussed below. Abrupt increases in urinary excretion may be expected if the toxic action of mercury causes an increase in exfoliation of renal tubular cells. Fecal excretion should represent both the dietary intake (including losses from dental amalgam) and biliary secretion. Scalp hair has been used to indicate a previous acute exposure to inorganic mercury (26). However, the extent of deposition in hair is far less than that of methyl mercury, which, owing to its presence in the diet, may confound attempts to monitor mer- curic mercury. There is a danger of external contamination depending upon the circumstances of exposure and some transfer to hair may occur via secretion of mercuric mercury in sweat. 2.3.2 Toxic Actions The lethal dose of mercuric chloride in humans is about 1 g. In the past mercuric chloride was available as an antiseptic, which led to its misuse as a suicidal agent. The ensuring acute gastrointestinal damage causes the victim to go into cardiovascular shock leading to renal failure and death. Chronic lower doses of inorganic mercury may cause renal damage by one of two different mechanisms: an indirect mechanism involving the immune system and a direct action on cells lining the kidney tubules. Mercury acts on the immune system leading to the production of antibodies that collect at and interact with the glomerular membrane of the kidney (for re- view, see ref. 5). The selective filtering action of the glomerulus is damaged Copyright © 2002 Marcel Dekker, Inc. allowing the passage of albumin into the glomerular filtrate and ultimately into urine. If the damage to the glomerular is sufficiently great, the protein loss results in the development of the full nephrotic syndrome with widespread edema, which can be life threatening. The nephrotic syndrome has been reported in people using skin whitening creams containing mercuric chloride as the active ingredient (27). Autopsy exam- ination has revealed the presence of antibodies laid down in glomerular tissue. Occupational exposure to high levels of aerosols of inorganic mercury has also produced the nephrotic syndrome (28). This immune-mediated mechanism of kidney damage has been reproduced in experiments, mainly using rats. The phe- nomenon is highly dependent on the strain of rat, the Brown Norway strain being the most susceptible (29). For information on exposure to lower levels over long periods, one has to turn to reports on occupational exposure to mercury vapor. At these lower levels, an increase in the urinary excretion of albumin may be detected. The amounts of albumin excreted are far less than those associated in the full-blown nephrotic syndrome. It is assumed that this is produced by the same immune mechanisms as that responsible for the nephrotic syndrome. However, recent experimental studies indicate that mercuric mercury can have direct effects on glomerular cells (30). Direct action on renal cells from acute doses of mercuric chloride given to rats can cause the loss of cells from the renal tubule especially in the more distal region of the proximal tubule. The original columnar-shaped cells are replaced by cuboid-shaped epithelial cells that resist the action of inorganic mercury. The animal becomes ‘‘tolerant’’ to subsequent doses of inorganic mercury. The major site of damage is the pars recta section of the proximal tubule (for review, see ref. 31). Intracellular thiols including glutathione and metallothionein are probably important defenses against the cytotoxic effects of inorganic mercury. Woods and Ellis (32) have suggested that resistance to the renotoxic effects of inorganic mercury (Hg ϩϩ ) is more closely related to capacity for upregulation of GSH syn- thesis than are elevated GSH levels per se. Piotrowski and Szumanska (33) dem- onstrate that inorganic mercury can induce metallothionen in kidney tissue. Chronic exposure to mercuric chloride given in the drinking water can also lead to kidney damage in rats such as loss in kidney weight. In the chronic toxicity test, no detailed examination of kidney function was undertaken (34). Evidence for direct effects on kidney cells at low chronic exposures comes from studies of occupational exposure to mercury vapor (see below). Two nonrenal effects of inorganic mercury have been reported. One report of occupational exposure to mercuric oxide aerosols claimed to find an associa- tion with effects on the peripheral nervous system with signs and symptoms simi- lar to those of amyotrophic lateral sclerosis (35). It is the only report of its kind. Copyright © 2002 Marcel Dekker, Inc. A second and much-better-documented effect is acrodynia or pink disease as discussed above. Prenatal damage has not been reported probably because this form of mercury does not cross the placenta. 2.4 Mercury Vapor 2.4.1 Disposition Mechanisms. Mercury vapor is a monatomic, electrically neutral gas pos- sessing high lipid solubility. Its oil-to-water partition is about 80 to 1 (18). It therefore passes readily across cell membranes and other diffusion barriers in the body in a fashion similar to other lipid-soluble gases such as the anesthetics. However, once inside the cells it is subject to oxidation to mercuric mercury. This oxidation step appears to be accomplished solely by the catalase-hydrogen peroxide reaction as follow: Cat-OH ϩ H 2 O 2 ϭ Cat-OOH ϩ H 2 O (1) Cat-OOH ϩ Hg 0 ϭ Cat-OH ϩ Hg ϩϩ ϩ 0 ϭ (2) Step (1) is the usual first step in the reaction of catalase (Cat-OH) with hydrogen peroxide to form the oxidant species catalase compound one (Cat-OOH). In step (2), catalase compound one removes two electrons from an atom of dissolved mercury vapor in a single transfer step (for details see ref. 36). This oxidation of mercury vapor to mercuric has been observed in red cells, liver, and brain homogenates. The availability of hydrogen peroxide is rate de- termining in red cells. Eventually all the vapor will be converted to mercuric mercury by this process. However, Magos (for a recent summary, see ref. 8) in a series of elegant animal experiments has demonstrated that vapor will persist in the bloodstream for a sufficient period to allow diffusion into all organs and tissues of the body. Observations on human subjects are consistent with this con- clusion (37). The persistence of vapor in the bloodstream undoubtedly accounts for marked difference in early tissue distribution as between inhaled vapor and ingested mercuric mercury. Toxicokinetics. Most of the quantitative data on the disposition of inhaled vapor comes from two studies on volunteers exposed for about 15–20 minutes to radio-labeled (37,38) and to nonlabeled mercury vapor (39). The retention of inhaled mercury vapor is about 80% of the amount inhaled. This is consistent with observations of occupationally exposed workers (40). Ac- cording to calculations by Magos (8), most of the retained vapor diffuses immedi- ately into the bloodstream. Approximately 8% of the retained dose is found in the blood compartment 24 h after exposure. Unlike exposure to mercuric mer- cury, more mercury is found in red cells rather than in plasma after vapor expo- sure. The red blood cell level is approximately twice the plasma level in early Copyright © 2002 Marcel Dekker, Inc. days following a single exposure. However, as mercury vapor is converted to mercuric mercury, the proportion found in red cells will diminish. About 7.1% of the inhaled dose is found in the head region according to external radioactive counting. Deposition in the kidneys is about 30% 3 days after, according to animal data exposure (18). As vapor is transformed to mercuric mercury, the proportion of the body burden found in kidneys increases. Elimination from the body occurs by exhalation of the vapor and via excre- tion of mercuric mercury in urine, faces, and sweat. Exhalation can account for as much as 7–14% of the inhaled dose. Urinary excretion is relatively low soon after exposure but rises as the amount of mercury in the kidneys increases. Thus urinary excretion is as low as 0.25% of the inhaled dose in the week following exposure as compared to 2% in the feces. In contrast, after long-term occupational exposure, urinary and fecal excretion rates are approximately the same. The half-times of elimination vary between tissues. Lung tissue has the fastest half-time of 1.7 days. This short half-time presumably involves a substan- tial proportion lost by exhalation. The blood compartment has two half-times, 2–4 days accounting for 90% and 15–30 days accounting for most of the remain- der. The kidney has the longest half-time of about 76 days. The half-time in the head regions is surprisingly short, of the order of about 19 days. Vapor after crossing the blood-brain barrier is presumable oxidized to mercuric mercury that should be effectively trapped as it passes across the blood- brain barrier much more slowly than does the vapor. Since this half-time was determined by radioactive counting of the head region, radioactivity in cerebral blood vessels may have contributed to this apparently rapid elimination. There is evidence from autopsy data for a much longer half-time in brain tissues, perhaps measured in years. Miners who had been retired for many years still had greatly elevated mercury levels at the time of their death (41,42). In the Kosta et al. study (42), the mercury levels in brain and other tissues from these miners were closely related to selenium levels. A WHO Expert Group (5) has suggested that mercuric mercury, after long-term residence in the body tissues, exists as an inert insoluble complex with selenium. Whole blood, plasma, and urine have been the most common media used for purposes of biological monitoring. As noted above, the red-cell-to-plasma ratio varies depending on the time after exposure. Having at least two elimination half-times complicates the blood compartment. Several elimination half-times have been reported in urine. As noted for mercuric mercury, urinary mercury derives directly and predominantly from the mercury in kidney tissues. If renal damage occurs leading to exfoliation of mercury-laden cells, urinary excretion might increase abruptly. For these reasons there is no ideal biological monitoring medium to indicate the body burden of levels of mercury in the target tissues, namely the brain and kidneys (see below). The problem is especially difficult in attempts to recapitulate Copyright © 2002 Marcel Dekker, Inc. episodic exposures. Hair has been used for mercuric and methyl mercury but, with exposure to vapor, external contamination will always be a problem. The picture is somewhat brighter for long-term exposures where the indi- vidual has achieved steady state. The elimination half-times quoted above would suggest that they should occur after about 1 year’s exposure except for the ex- tremely long half-time. However, the latter may reflect a nontoxic form of mer- cury and this may not be important for biological monitoring to assess risks of toxicity. Thus it has been possible to demonstrate linear quantitative relationship between air levels determined by personal monitors and the corresponding blood levels and urinary excretion rates in chronically exposed workers (for details see ref. 8). These relationships are as follows: B-Hg ϭ 6.4 ϩ 0.48 ϫ A-Hg where B-Hg is the mercury concentration in blood expressed as micrograms per liter and A-Hg is the air concentration determined by personal samplers. U-Hg ϭ 10.2 ϩ 1.01 ϫ |A-Hg where U-Hg is the urinary excretion rate expressed as micrograms of mercury per gram creatinine in urine. The creatinine correction is frequently applied to measurements of urinary mercury to correct for variations in urinary flow rates. Creatinine is produced at an approximately steady state in muscle tissues, filtered via the glomerulus, and excreted unchanged in urine. Approximated 1.6 g of creatinine are excreted in 24 h in the average adult. Thus the amount of mercury in urine associated with 1 g of creatinine corresponds to the amount of mercury excreted in 24/1.6 ϭ 15 h. Compared to using the observed concentration of mercury in urine, which may vary according to urinary flow rates, the creatinine correction provides more reli- able, less variable data (43). Actually the rate of creatinine excretion is closely proportional to the lean body mass (44). Today, weighing scales are available that will directly determine lean body mass thus opening up the possibility that the true creatinine excretion rate can be determined on an individual basis rather that assuming a constant number for everyone. One report on workers occupationally exposed to mercury vapor noted that concentrations in saliva parallel blood levels (45). If confirmed, these findings indicate a useful future role for saliva as a biological monitoring medium 2.4.2 Toxic Actions Mercury vapor can cause acute damage to the lungs and death from pneumonia when inhaled at extremely high concentrations. Goldwater (46) has reviewed numerous case reports of mercury-induced pneumonitis but where accurate data on air levels are lacking. Mercury vapor was inhaled as a treatment for syphilis up to the early years of the twentieth century. Careful measurements by Engelbreth Copyright © 2002 Marcel Dekker, Inc. [...]... probably reflecting difference in the degree of binding to hemoglobin The levels in the fetal brain are similar to those in the mother as determined from animal data Methyl mercury is avidly accumulated in human scalp hair during the process of formation of the hair in the follicular cells Concentrations of methyl mercury in newly formed hair parallel those in blood Methyl mercury concentrations in the hair... recruited in 1987– 88 The recruitment of the main study cohort is of similar size as the pilot group was started and completed in 1989 The experience with the pilot group was used to guide the experimental design of the main cohort The offspring of the mothers in each cohort have been subjected to a range of developmental tests appropriate to the age of the child In the main study the children were examined... the predominant mercury species in the blood compartment Inorganic mercury gradually became an increasing fraction of total mercury in the body It was the predominant form in urine and feces The pharmacokinetic data on the disposition of methyl mercury in adult humans allows the derivation of a quantitative relationship between the daily ingested dose of methyl mercury and the corresponding hair and... excess of 10 ppm Another study on an ocean-fish-eating population was also conducted in the 1980s in coastal villages in Peru (128) The villages were isolated by a coastal desert from large towns and industries, so local pollution was minimal Ocean fish, consumed regularly, was the main source of protein This study involved 131 infant-mother pairs having mean methyl mercury levels in pregnancy of 8.3... will bind to other ligands with the possible exception of the selenide form of selenium (R-Se Ϫ) (63) Thus methyl mercury is found in tissues and biological fluids bound to protein- and thiol-containing amino acids and peptides such as cysteine and reduced glutathione (reviewed in ref 4) Methyl mercury attached to l-cysteine is transported into the endothelial cells of the blood capillaries on the neutral... within the brain cannot be explained by selective deposition of methyl mercury In general, the brain levels are, if anything, somewhat below the average for other tissues (91) Likewise the same authors reported that levels of methyl mercury within the brain showed no correlation with areas of damage The first biochemical evidence of brain damage came from early studies in Japan in the 1960s Yoshino... consuming First Nations people living in Northern Canada, experienced marked seasonal changes in hair levels The highest level is achieved in late summer and early fall when weather conditions prevent further fishing The lowest levels occur just before next year’s fishing season (110) Seasonal changes are indicated in this population by differences in average mercury levels in the 9-cm versus the greater-than-20-cm... Apparently it binds to the thiol ligands of the tubulin monomers and prevents their assembly at the growing end of the microtubule Microtubules are continuously assembled at one end and depolymerized at the other in a treadmilling process Blocking only the assembly process allows the Copyright © 2002 Marcel Dekker, Inc depolymeriztion process to continue so that the microtubule eventually disappears The depolymerization... cells as urinary excretion of tubular antigens and enzymes was increased in the exposed group The renal effects were mainly found in workers excreting more than 50 µg Hg/g creatinine Mechanisms: These early biochemical markers of kidney function reflect the sub- or preclinical effects of inorganic mercury They probably result from the action of inorganic mercury on the brush border membranes of the tubular... respectively The mean urine levels in the male and female workers were 52 µg Hg/g creatinine and 37 Hg/g creatinine, respectively The control groups had mean urine mercury levels of 0.9 µg Hg/g creatinine for men and 1.7 Hg/g creatinine for women Most measures of renal function did not differ between the exposed and nonexposed groups, e.g., urinary excretion of amino acids, total protein albumin, and β 2-microglobulin, . maternal blood probably reflecting differ- ence in the degree of binding to hemoglobin. The levels in the fetal brain are similar to those in the mother as determined from animal data. Methyl. the infant having pink cheeks and hands, being photophobic, and experiencing joint pain sufficiently severe to cause the child to cry and complain frequently. In fact, the constant crying by the. remain- der. The kidney has the longest half-time of about 76 days. The half-time in the head regions is surprisingly short, of the order of about 19 days. Vapor after crossing the blood-brain barrier