Circadian rhythms in the urinary excretion of metals and organic substances in "healthy" men

Circadian rhythms in the urinary excretion of metals and organic substances were examined in ten "healthy" men under conditions of water loading and restriction. Four characteristic rhythms were observed: (1) decreased excretion during the night for lead and urinary flow rate; (2) decreased excretion of hippuric acid, delta-aminolevulinic acid, coproporphyrin, creatinine, and total urinary solutes during the night and morning hours; (3) increased excretion of mercury and zinc during the morning hours; and (4) no significant variation for copper. Excretion of lead, hippuric acid, delta-aminolevulinic acid, and total urinary solutes was significantly correlated with urinary flow rate and creatinine excretion, which suggested that their circadian rhythms were the consequence of reduced glomerular filtration and increased reabsorption by the distal tubule and collecting duct during the night and morning hours. Similarly, it was suggested that the mercury and zinc rhythms resulted partly from increased reabsorption during the night hours; the coproporphyrin rhythm reflected reduced glomerular filtration of coproporphyrinogen during the night and morning hours.     

Circadian rhythms of seven heavy metals in plasma, erythrocytes and urine in men: observation in metal workers

To elucidate circadian rhythms (variation within a day) of 7 toxic or essential metals in plasma and erythrocytes in relation to the rhythms in urine in men, 19 male metal foundry workers were examined; they were exposed to lead (Pb), zinc (Zn) and copper (Cu) occupationally but separated from the exposure during the study. Circadian rhythms were found for plasma concentration of Pb, cadmium (Cd), Zn, Cu and chromium (Cr) in the workers. Circadian rhythms were also found for Pb, inorganic mercury (Hg), Zn and Cr in erythrocytes and for all metals except Zn in urine. Both the plasma and urinary levels of Pb, Cd, Cu and Cr together with urinary excretion of Mn and creatinine tended to decrease during night hours; both the erythrocyte and urinary levels of Hg together with both the plasma and erythrocyte levels of Zn tended to increase during morning hours. The results of profile analysis suggested that the circadian rhythm of Pb in urine was affected more strongly by its plasma and erythrocyte rhythms than by the rhythm of creatinine in urine, i.e. the rhythm of glomerular filtration; the urinary rhythms of Cd, Cr, and Mn were affected more by the creatinine rhythm; and the urinary rhythm of Cu was affected by both its plasma and creatinine rhythms. On the other hand, the urinary rhythm of Hg was assumed to be independent of the creatinine rhythm and be affected by its erythrocyte rhythm. The present study suggested that different biological limit values might be needed for different hours of the day especially for shift workers who are exposed to various heavy metals. Instead, further studies should be conducted to find the adjustment methods by which no circadian rhythms are discerned.     

Filterable plasma concentration, glomerular filtration, tubular balance, and renal clearance of heavy metals and organic substances in metal workers

To estimate "filterable" plasma concentration (FPx), glomerular filtration, tubular balance, and renal clearance of heavy metals and organic substances, the authors examined the regressions of the 24-hr urinary excretion on glomerular filtration rate [GFR, 24-hr endogenous creatinine (Cn) clearance] in 19 gun-metal foundry workers with blood lead (Pb) concentrations of 25-59 micrograms/dl. It was estimated that the proportion of FPx to total plasma concentration was on average 15, 7, 3, 0.6, 0.06, and 0.008% for Pb, cadmium (Cd), manganese (Mn), zinc (Zn), chromium (Cr), and copper (Cu), respectively. The estimated FPx value was 2.8 X 10(2), 4, 0.08, and 2.8 X 10(4) micrograms/dl for hippuric acid (HA), delta-aminolevulinic acid (ALA), coproporphyrin (CP), and total urinary solutes (TUS), respectively. The estimated glomerular filtration was significantly greater than the zero level for all substances but inorganic mercury (Hg). Similarly, the estimated net tubular secretion was significantly greater than the zero level for Cr, Cu, and TUS; the net tubular reabsorption was significantly greater than the zero level for Pb, ALA, and CP. The renal clearance of "filterable" plasma substance was significantly greater than GFR for Cr, Cu, and TUS and was significantly smaller for Pb, ALA, and CP. Thus the renal excretory mechanisms of substances were classified into four major categories: glomerular filtration for Cd, Mn, Zn, HA, and Cn; glomerular filtration and net tubular secretion for Cr, Cu, and TUS; glomerular filtration and net tubular reabsorption for Pb, ALA, and CP; and no glomerular filtration, i.e., suspected tubular secretion, for Hg.     

Filterable Plasma Concentration,Glomerular Filtration,Tubular Balance,and Renal Clearance of Heavy Metals and Organic Substances in Metal Workers

To estimate “filterable” plasma concentration (FPx), glomerular filtration, tubular balance, and renal clearance of heavy metals and organic substances, the authors examined the regressions of the 24-hr urinary excretion on glomerular filtration rate [GFR, 24-hr endogenous creatinine (Cn) clearance] in 19 gun-metal foundry workers with blood lead (Pb) concentrations of 25–59 μg/dl. It was estimated that the proportion of FPx to total plasma concentration was on average 15,7,3,0.6,0.06, and 0.008% for Pb, cadmium (Cd), manganese (Mn), zinc (Zn), chromium (Cr), and copper (Cu), respectively. The estimated FPx value was 2.8 × 10², 4,0.08, and 2.8 × 10⁴ μg/dl. for hippuric acid (HA), delta-aminolevulinic acid (ALA), coproporphyrin (CP), and total urinary solutes (TUS), respectively. The estimated glomerular filtration was significantly greater than the zero level for all substances but inorganic mercury (Hg). Similarly, the estimated net tubular secretion was significantly greater than the zero level for Cr, Cu, and TUS; the net tubular reabsorption was significantly greater than the zero level for Pb, ALA, and CP. The renal clearance of “filterable” plasma substance was significantly greater than GFR for Cr, Cu, and TUS and was significantly smaller for Pb, ALA, and CP. Thus the renal excretory mechanisms of substances were classified into four major categories: (1) glomerular filtration for Cd, Mn, Zn, HA, and Cn; (2) glomerular filtration and net tubular secretion for Cr, Cu, and TUS; (3) glomerular filtration and net tubular reabsorption for Pb, ALA, and CP; and (4) no glomerular filtration, i.e., suspected tubular secretion, for Hg.     

Adjustment of creatinine-adjusted values in urine to urinary flow rate: a study of eleven heavy metals and organic substances

The use of urinary monitoring in medical surveillance programs in industry requires development of an accurate and unbiased index of urinary concentrations of occupational toxins. To examine the effects of urinary flow (UF) rate on the standard creatinine (Cn)-adjusted value and the UF- and Cn-adjusted values according to Greenberg and Levine and to Araki et al. for 11 heavy metals and organic substances, 19 metal-foundry workers aged 34–59 years (mean 48), who had been exposed to lead, zinc, and copper for 2–17 (mean 10) years, were studied during four periods of the day under water-free, water-restrictive and water-loading conditions for 6 days. The blood lead concentrations of the 19 workers ranged from 22 to 59 (mean 38) g/dl. The results indicated that there was no significant OF effect on the UF- and Cn-adjusted values of Araki et al. for all urinary substances except mercury and coproporphyrin. On the other hand, the UF- and Cn-adjusted value of Greenberg and Levine was positively correlated with OF rate for all urinary substances, and the standard Cn-adjusted value was either positively or inversely correlated with OF rate for many urinary substances. Therefore, the UF- and Cn-adjusted value of Araki et al. is considered to be applicable to the measurement of most urinary substances under conditions of wide variation in OF rate.     

Effects of water restriction and water loading on daily urinary excretion of heavy metals and organic substances in metal workers.

The effects of urinary volume on daily urinary excretion of seven heavy metals and four organic substances were examined in relation to the changes in their plasma and erythrocyte concentrations and urinary creatinine excretion in 19 metal workers. The examination was conducted under the conditions of water restriction and loading for six days. The major findings were as follows: (1) urinary excretion of all heavy metals and organic substances except mercury, together with creatinine excretion, significantly decreased under the water restrictive condition whereas under the water loading condition their excretion significantly increased and (2) daily variations in urinary excretion of lead, cadmium, chromium, copper, hippuric acid, delta-aminolaevulinic acid, and coproporphyrin did not differ significantly from the variation in urinary excretion of creatinine (profile analysis, p greater than 0.05). It is suggested that glomerular filtration is the major factor determining renal excretory mechanisms of the four heavy metals and three organic substances examined.     

Effects of water restriction and water loading on daily urinary excretion of heavy metals and organic substances in metal workers

The effects of urinary volume on daily urinary excretion of seven heavy metals and four organic substances were examined in relation to the changes in their plasma and erythrocyte concentrations and urinary creatinine excretion in 19 metal workers. The examination was conducted under the conditions of water restriction and loading for six days. The major findings were as follows: (1) urinary excretion of all heavy metals and organic substances except mercury, together with creatinine excretion, significantly decreased under the water restrictive condition whereas under the water loading condition their excretion significantly increased and (2) daily variations in urinary excretion of lead, cadmium, chromium, copper, hippuric acid, delta-aminolaevulinic acid, and coproporphyrin did not differ significantly from the variation in urinary excretion of creatinine (profile analysis, p greater than 0.05). It is suggested that glomerular filtration is the major factor determining renal excretory mechanisms of the four heavy metals and three organic substances examined.     

Adjustment of urinary concentration to urinary volume in relation to erythrocyte and plasma concentrations: an evaluation of urinary heavy metals and organic substances

The effects of urinary volume on adjusted and nonadjusted urinary excretion of 11 heavy metals and organic substances were examined in relation to plasma and erythrocyte concentrations in 19 metal workers under conditions of water restriction and loading. Blood lead concentrations in these workers ranged from 25 to 59 micrograms/dl. The results indicated that: urinary volume significantly affects not only nonadjusted urinary concentration for all substances, but also affects timed excretion and concentrations adjusted to urinary specific gravity and to urinary creatinine for most substances; the concentration adjusted to urinary volume is, on the other hand, independent of urinary volume; and urinary excretion of lead and mercury is related more closely to erythrocyte concentration than to plasma concentration. This last finding reflects complex renal excretory mechanisms for these heavy metals.     

Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators

To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings.     

Letters to the Editor

The effects of urinary volume on adjusted and nonadjusted urinary excretion of 11 heavy metals and organic substances were examined in relation to plasma and erythrocyte concentrations in 19 metal workers under conditions of water restriction and loading. Blood lead concentrations in these workers ranged from 25 to 59 μg/dl. The results indicated that: (1) urinary volume significantly affects not only nonadjusted urinary concentration for all substances, but also affects timed excretion and concentrations adjusted to urinary specific gravity and to urinary creatinine for most substances; (2) the concentration adjusted to urinary volume is, on the other hand, independent of urinary volume; and (3) urinary excretion of lead and mercury is related more closely to erythrocyte concentration than to plasma concentration. This last finding reflects complex renal excretory mechanisms for these heavy metals.     

Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators.

To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings.     

Seadragon VI: a 7-day dry saturation dive at 31 ATA. IV. Circadian analysis of body temperature and renal functions

Circadian rhythms of body temperature and daytime rhythms of urine flow and urinary excretion of electrolytes were investigated in 4 male subjects before, during, and after a 7-d stay in a dry heliox 31 ATA environment. The chamber temperature was maintained at about 28 degrees C during pre- and postdive 1 ATA periods and was raised to 31.5 degrees C at 31 ATA. The circadian rhythm of the rectal temperature, as analyzed by the cosinor fitting method, showed the same mesor (the mean level of fluctuation) and the amplitude at 31 and 1 ATA. However, a reversible phase shift was noted at 31 ATA in which the acrophase shifted to 1435 h at 31 ATA from 1540 h (predive) or 1610 h (postdive) at 1 ATA. This shift was attributed to an early rise of rectal temperature during night at 31 ATA. A similar phase shift was observed at 31 ATA for the skin temperature of the forehead, a region not covered by clothing or blanket. The daytime rhythms of urinary excretion of water, Na, Cl, urea, and total osmotic substances were similar, with the acrophase at 1300-1500 h at both 1 and 31 ATA. On the other hand, the daytime rhythm for urinary excretion of K, which was similar to the above at 1 ATA, disappeared at 31 ATA. The urinary excretion of endogenous creatinine remained constant during both daytime and nighttime at both 1 and 31 ATA. These results suggest that exposure to 31 ATA may alter the underlying pattern of circadian or daytime rhythms for thermoregulatory and certain renal functions.     

Biliary and urinary excretion of metals in humans

Fifteen metals (lead, cadmium, arsenic, inorganic mercury, organic mercury, iron, manganese, magnesium, chromium, zinc, copper, nickel, cobalt, tin, and aluminum) were determined in the hepatic bile and urine collected simultaneously from three Japanese individuals (2 males, 1 female). The presence of these metals was classified as follows: hepatic biliary concentrations were higher than urinary concentrations (lead, arsenic, and iron); urinary concentrations were higher than hepatic biliary concentrations (cadmium, inorganic mercury, tin, cobalt, magnesium, chromium, copper, zinc, and nickel); hepatic biliary concentrations were almost equal to urinary concentrations (manganese and organic mercury); and relationship between hepatic biliary and urinary concentrations changed occasionally (aluminum). Eight essential metals (iron, manganese, magnesium, zinc, chromium, copper, nickel, and cobalt) were detected at considerable concentrations in hepatic bile. Accounting for the daily flow volume of hepatic bile and the reabsorption of these metals, the supplementation of these metals should occur during treatment of diseases accompanied by loss of hepatic bile.     

Urinary excretion of zinc, copper and iron in the streptozotocin-diabetic rat

The influence of the chemically diabetic condition on urinary excretion of zinc, copper and iron was investigated. Male Sprague-Dawley rats were injected with streptozotocin to induce insulin-dependent diabetes (day 0) and 24-hour urinary collections taken 1, 4, 7, 10 and 14 days later. Onset of the diabetic condition was correlated with a rapid and persistent increase in the amounts of the three trace metals excreted daily in the urine. Diabetic rats excreted 3.4-, 5.0- and 4.9-fold more zinc, copper and iron, respectively, than controls in the urine on day 14. Insulin treatment of diabetic rats significantly reduced the quantities of the micronutrients excreted in urine, suggesting that altered hormonal status was the primary cause of increased urinary losses. Enhanced urinary output of the metals was not associated with reduction in the plasma, liver and kidney contents of zinc, copper and iron. Urinary trace metal excretion was correlated with food ingestion and urinary volume with greater amounts lost during the dark period for control and diabetic animals. The influence of endocrine status on urinary excretion of trace metals is discussed.     

The effects of CaEDTA injection on lead,zinc, copper and ALAD in erythrocyte,plasma and urine in lead-exposed workers: a 24-h observation

Summary To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the concentrations of lead, zinc and copper in plasma, erythrocyte and urine, and the delta-aminolevulinic acid dehydratase (ALAD) activity in erytrocyte, we administered CaEDTA in 1-h intravenous infusion to ten male gun metal founders with blood-lead concentration of 39 to 64 g/dl (mean 49 g/dl). We found that the plasma concentration of lead, following a rapid rise within the first 3 h, fell temporarily to the level significantly lower than the initial level 19 h after start of the infusion. The plasma concentration of zinc fell to the minimal level 5 h after the infusion; and the erythrocyte concentration of zinc and the ALAD activity concurrently rose to the maximal level 5 h after the infusion. By contrast, no significant alteration was observed in the concentrations of copper in plasma and erythrocyte. The maximal level of urinary metal excretion was attained during the period between 1 and 2 h after start of CaEDTA infusion for lead; within 2 h for zinc; and between 2 and 4 h for copper. The urinary metal excretion returned to the initial level 14 to 24 h after infusion for zinc and copper; but lead excretion was still higher than the initial level during this period. The difference in the kinetics of the three metals following CaEDTA injection is discussed in the light of these findings.     

Adjustment for urinary flow rate: an improved approach to biological monitoring

Summary The use of urinary monitoring in medical surveillance programs in industry requires the development of an accurate and unbiased index of urinary concentrations of occupational toxins. To examine the effects of urinary flow rate on adjusted and non-adjusted urinary excretion of 11 heavy metals and organic substances, 19 metal-foundry workers were studied during four time periods of the day under conditions of water restriction and loading. The results indicate that urinary flow rate significantly affects not only the non-adjusted urinary concentration for all substances, but also affects timed excretion as well as concentrations adjusted to urinary specific gravity and to urinary creatinine during any time period of the day. On the other hand, the concentration adjusted to urinary flow rate (UF-adjusted concentration) is independent by definition of urinary flow; therefore, this adjustment is applicable for highly diluted and highly concentrated urine samples without repetition of urine collection. It is concluded that UF-adjusted concentration is a useful index for the measurement of most urinary substances, while adjustments to urinary specific gravity and to urinary creatinine concentration have only limited utility in evaluating toxin levels in spot urine samples.     

广州市场食用鱼中5种重金属含量分析及评价

目的:评价市场上常见食用鱼的重金属(锌、铅、镉、铜、铬)污染状况和食用安全性。方法:采用硝酸-高氯酸消化和火焰原子吸收法对广州市场21种鱼中重金属含量进行分析及评价。结果:21种鱼中重金属含量符合以下规律:必需微量元素锌、铜、铬含量较高,非必需微量元素铅含量较低,镉未检出;根据《NY 5073-2006无公害食品水产品中有毒有害物质限量》,所测样品的铅、镉、铜未超标;鳗鱼中的铬含量超过"人体消费卫生标准"。结论:鳗鱼中的铬含量较高,经常食用存在潜在危害,应引起有关部门重视。     

Circadian rhythm of blood and urinary copper in presumably healthy subjects of vegetarian food habit

Circadian rhythm of blood and urinary copper has been studied in presumably healthy subjects of a particular ethnic group in India who are vegetarians. A definite 24-hr variation has been observed for both blood and urinary copper. The peak for blood copper was 1,500 hr and the lowest value was 0600 hr, with values of 0.185 mg/100 ml and 0.106 mg/100 ml respectively. The urinary peak and trough occurred at 0600 and 0300 hr, respectively. Remarkably higher 24-hr copper excretion values were noted (64.49 micrograms/day) with a range of 15-100 micrograms/day. The blood level of copper (0.134 mg/100 ml) remained within the range reported. One subject out of 25 deviated from the group with respect to circadian phasing and amplitude to urinary copper excretion.     

Metal cotolerance to cooper,lead, and zinc in Festuca rubra

Tillers of red fescue (Festuca rubra) were collected from three copper-contaminated sites: Prescot (Lancashire, near the copper refinery factory), Great Orme (Clwyd, copper mine), and Ecton (Staffordshire, copper mine), as well as from an uncontaminated area (Festuca rubra S59). By comparing their indexes of tolerance, it was discovered that tillers from Ecton which contained a rather high level of copper, lead, and zinc were tolerant to all three metals. This variety of F. rubra would be useful for reclaiming nonferrous mine spoils which contain a high level of the three commonly occurring heavy metals, i.e., copper, lead and zinc.     

Effects of harmful trace elements on iron, zinc and copper: their interactions in animals and humans. II. Lead]

Toxic effect of lead is related, among others, to metabolic interactions with essential trace elements i.e. iron, zinc and copper. Lead stimulates urinary excretion of these elements interfering with their reabsorption in kidney as well as inhibits ceruloplasmin activity in plasma, ferrochelatase activity in reticulocytes and copper- and zinc-dependent superoxide dismutase activity in tissues--with all functional consequences for organism. Iron, zinc and copper deficiency results in increased lead toxicity through considerable enhancement of lead absorption from intestinal tract, producing greater degree of anemia as well as decreasing of metalloenzymes activity. Increasing dietary zinc and probably copper suppresses intestinal absorption of lead. The addition of iron, zinc and copper to the diet prevents lead accumulation within the tissues and subsequent toxicity of this element. It seems that increasing intake of food products containing a lot of essential trace elements can diminish risk of lead toxicity for human.